2 3 8 U N I T I I Diseases of Organ Systems most useful in deciding if her cancer may benefit from therapy
targeting a tyrosine kinase?
65 A 64-year-old man, who is a chain-smoker, has had a A Amplification of FGFR1 gene
cough and a 5-kg weight loss over the past 3 months. Physi- B Inactivation of CDKN2A gene
cal examination shows clubbing of the fingers. He is afebrile. C Loss of both copies of TP53
A chest radiograph shows no hilar adenopathy, but there is D Mutation in K-RAS gene
cavitation within a 3-cm lesion near the right hilum. Labora- E Rearrangement of ALK gene
tory studies show a serum calcium of 12.3 mg/dL, phospho-
rus of 2.4 mg/dL, and albumin of 3.9 g/dL. Bronchoscopy
shows a lesion almost occluding the right main bronchus. A
surgical procedure with curative intent is attempted. Which
of the following neoplasms is most likely to be present in
this patient?
A Adenocarcinoma in situ
B Kaposi sarcoma
C Large cell anaplastic carcinoma
D Metastatic renal cell carcinoma
E Non-Hodgkin lymphoma
F Small cell anaplastic carcinoma
G Squamous cell carcinoma
66 A 79-year-old woman has had increasing malaise and a 68 A 60-year-old woman has had a chronic nonproduc-
5-kg weight loss over the past 5 months. She has had a chronic tive cough for 4 months along with loss of appetite and a 6-kg
nonproductive cough for 3 months. On physical examination, weight loss. She does not smoke. On physical examination
she has no abnormal findings. Pulmonary function tests are there are no remarkable findings. Her chest radiograph shows
normal. Her peripheral blood counts are normal. Her chest a right peripheral subpleural mass. A fine-needle aspiration
radiograph is shown in the figure. What is a biopsy of one of biopsy is performed, and she undergoes a right lower lobec-
her lung lesions most likely to show? tomy. The microscopic appearance of the lesion is shown in
A Adenocarcinoma the figure. She receives immunotherapy directed at epithelial
B Granulomatous inflammation growth factor receptor (EGFR) and remains symptom-free for
C Necrotizing vasculitis the next 10 years. Which of the following neoplasms did she
D Organizing abscess most likely have?
E Silica crystals A Adenocarcinoma
B Bronchial carcinoid
67 A 45-year-old woman, a nonsmoker, has had a chronic C Hamartoma
nonproductive cough for 6 months along with 8-kg weight D Large cell carcinoma
loss. On physical examination there are no remarkable find- E Small cell anaplastic carcinoma
ings. Her chest radiograph shows a right peripheral subpleu- F Squamous cell carcinoma
ral mass. A fine-needle aspiration biopsy is performed, and
she undergoes a right lower lobectomy. The microscopic ex- 69 A 50-year-old man has developed truncal obesity, back
amination of the lesion shows glands invading the surround- pain, and skin that bruises easily over the past 5 months. On
ing lung. Which of the following molecular test findings is physical examination, he is afebrile, and his blood pressure
is 160/95 mm Hg. A chest radiograph shows an ill-defined,
4-cm mass involving the left hilum of the lung. Cytologic ex-
amination of bronchial washings from bronchoscopy shows
round epithelial cells that have the appearance of lymphocytes
but are larger. The patient is told that, although his disease is
apparently localized to one side of the chest cavity, surgical
treatment is unlikely to be curative. He also is advised to stop
smoking. Which of the following neoplasms is most likely to
be present in this patient?
A Adenocarcinoma
B Bronchial carcinoid
C Bronchioloalveolar carcinoma
D Large cell carcinoma
E Non-Hodgkin lymphoma
F Small cell anaplastic carcinoma
G Squamous cell carcinoma
70 A 57-year-old woman has had a cough and pleuritic C H A P T E R 1 5 The Lung 2 3 9
chest pain for the past 3 weeks. On physical examination, she
is afebrile. Some crackles are audible over the left lower lung 72 A 72-year-old woman has had difficulty with vision in
on auscultation. A chest radiograph shows an ill-defined area her right eye for 3 months. She also has pain in the right upper
of opacification in the left lower lobe. After 1 month of antibi- chest. The findings on physical examination include unilateral
otic therapy, her condition has not improved, and the lesion enophthalmos, miosis, anhidrosis, and ptosis on the right side
is still visible radiographically. CT-guided needle biopsy of of her face. A chest radiograph shows right upper lobe opacifi-
the left lower lobe of the lung is performed, and the specimen cation and bony destruction of the right first rib. Which of the
has the histologic appearance shown in the figure. Which of following conditions is most likely to be present in her?
the following neoplasms is most likely to be present in this A Bronchopneumonia
patient? B Bronchiectasis
A Adenocarcinoma in situ C Bronchogenic carcinoma
B Large cell anaplastic carcinoma D Sarcoidosis
C Malignant mesothelioma E Tuberculosis
D Metastatic breast carcinoma
E Squamous cell carcinoma 73 A 43-year-old woman has never smoked and works as a
file clerk at a university that designates all work areas as non-
71 A 59-year-old man who has smoked one pack of ciga- smoking. A routine chest radiograph shows a 3-cm, sharply
rettes per day for the past 43 years has developed a severe demarcated mass in the left upper lobe of the lung. Fine-
cough with hemoptysis over the past month. He has expe- needle aspiration of the mass is attempted, but the patholo-
rienced a 10-kg weight loss over the past year. On physical gist performing the procedure remarks, “This is like trying to
examination, he is afebrile. Laboratory studies show a serum biopsy a ping-pong ball.” No tissue is obtained. Thoracotomy
Na+ of 120 mmol/L; K+, 3.8 mmol/L; Cl–, 90 mmol/L; CO2, 24 with wedge resection is performed. On sectioning, the mass
mmol/L; glucose, 75 mg/dL; creatinine, 1.2 mg/dL; calcium, has a firm, glistening, bluish white cut surface. A culture of
8.1 mg/dL; phosphorus, 2.9 mg/dL; and albumin, 4.2 g/dL. the mass yields no growth. This mass most likely represents
Which of the following findings is most likely to be seen on a which of the following?
chest radiograph? A Adenocarcinoma
A Bilateral upper lobe cavitation B Hamartoma
B Diaphragmatic pleural calcified plaques C Large cell carcinoma
C Extensive areas of infiltrates D Mesothelioma
D Invasive perihilar mass E Non-Hodgkin lymphoma
E Pneumothorax F Squamous cell carcinoma
F Subpleural nodule with hilar adenopathy
G Upper lung nodule with air-fluid level 74 A 40-year-old man has had an increasing cough with he-
moptysis for 2 weeks. He has never smoked and is in very good
health. On physical examination, his temperature is 38.2° C. A
chest radiograph shows an area of consolidation in the right
upper lobe. His condition improves with antibiotic therapy;
however, the cough and hemoptysis persist for 2 more weeks.
Chest CT scan now shows right upper lung atelectasis. Bron-
choscopic examination shows a tan, circumscribed obstructive
mass filling a right upper lobe bronchus. Which of the follow-
ing neoplasms is most likely to produce these findings?
A Adenocarcinoma
B Carcinoid tumor
C Hamartoma
D Kaposi sarcoma
E Large cell carcinoma
75 A 24-year-old man has had increasing dyspnea for the
past 10 weeks. On physical examination, he is afebrile. There is
dullness to percussion over the lungs posteriorly and d ecreased
breath sounds. A chest radiograph shows large bilateral pleu-
ral effusions and widening of the mediastinum. Thoracentesis
is performed on the left side and yields 500 mL of milky white
fluid. Laboratory studies of the fluid show a high protein con-
tent; microscopy shows many lymphocytes and fat globules.
What is the most likely cause for these findings?
A Bacterial pneumonia with empyema
B Congenital heart disease with congestive failure
C Marfan syndrome with aortic dissection
D Micronodular cirrhosis with hypoalbuminemia
E Miliary tuberculosis with granulomatous pleuritis
F Non-Hodgkin lymphoma with lymphatic
obstruction
2 4 0 U N I T I I Diseases of Organ Systems Inhalation of which of the following pollutants is the most
likely factor in the pathogenesis of this mass?
76 A 68-year-old man has had increasing dyspnea with A Asbestos
cough productive of frothy sputum for the past 5 months. On B Bird dust
physical examination, he is afebrile, and his blood pressure C Coal dust
is 165/100 mm Hg. There is dullness to percussion at lung D Cotton fibers
bases. He has pitting edema of the ankles. A chest radiograph E Ozone
shows blunting of costophrenic recesses bilaterally and car- F Silica
diomegaly with prominent right and left heart borders. A
right thoracentesis is performed, and 300 mL of straw-colored 78 A 47-year-old woman, a non-smoker, has a 4-month his-
fluid is removed. Laboratory studies on this fluid show total tory of mild but persistent right-sided chest pain. On physical
protein of 2.2 g/dL (serum is 6.5 g/dL), glucose of 45 mg/dL examination, there are no remarkable findings. A chest radio-
(serum is 75 mg/dL), lactate dehydrogenase of 200 U/L (se- graph shows a pleural mass on the right side. No pleural effu-
rum is 420 U/L), pH 7.2, and cell count of 100/mm3 mononu- sions are seen. Chest CT scan shows a localized, circumscribed
clear leukocytes, and no RBCs. What condition does he most 3 × 7 cm mass attached to the visceral pleura; the lungs and
likely have? chest wall appear normal. At thoracotomy, the mass is excised.
A Cavitary tuberculosis On microscopic examination, the mass is composed of spin-
B Congestive heart failure dle cells resembling fibroblasts with abundant collagenous
C Malignant mesothelioma stroma. With immunohistochemical staining, the spindle cells
D Non-Hodgkin lymphoma mark for CD34, but are cytokeratin-negative. There has been
E Pneumococcal pneumonia no recurrence of the lesion. Which of the following is the most
F Small cell carcinoma likely diagnosis?
77 A 78-year-old man has had increasing dyspnea without A Bronchioloalveolar carcinoma
cough or increased sputum production for the past 4 months. B Hamartoma
On physical examination, he is afebrile. Breath sounds are C Hodgkin lymphoma, nodular sclerosis type
reduced in all lung fields. A chest CT scan shows a dense, D Malignant mesothelioma
brightly attenuated pleural mass encasing most of the left E Metastatic breast carcinoma
lung. Microscopic examination of a pleural biopsy specimen F Solitary fibrous tumor
shows spindle and cuboidal cells that invade adipose tissue.
ANSWERS unlikely from trauma alone; hemorrhage is more likely. Inter-
stitial disease would produce more opacity, not less.
1 A An extralobar sequestration produces an external
mass effect upon normal lung and limits gas exchange be- PBD9 671 BP9 460 PBD8 732 BP8 535
cause it is not connected to airways and has an anomalous
systemic arterial connection. Intralobar sequestrations with- 3 E Resorption atelectasis is most often the result of a
in lung parenchyma typically are diagnosed in childhood mucous or mucopurulent plug obstructing a bronchus. Air
in association with recurrent infections. Foregut cysts in the in alveoli distal to the obstruction is resorbed and that por-
hilum or mediastinum are not connected to airways and can tion of lung collapses. This can occur postoperatively, or it
produce a mass effect if large, but most are not. The term may complicate bronchial asthma. Compression atelectasis
gestation likely excludes pulmonary immaturity with lack results from accumulation of air or fluid in the pleural cav-
of surfactant. The normal amount of amniotic fluid excludes ity, which can happen with a pneumothorax, hemothorax, or
the oligohydramnios sequence that often leads to pulmonary pleural effusion. Contraction atelectasis occurs when fibrous
hypoplasia. A tracheoesophageal fistula predisposes to pul- scar tissue surrounds the lung. Microatelectasis can occur
monary infection. postoperatively, in diffuse alveolar damage, and in respira-
tory distress of the newborn from loss of surfactant. Relax-
PBD9 670 BP9 460 PBD8 732 BP8 535 ation atelectasis is a synonym for compression atelectasis.
2 D Blunt trauma to the chest can lead to rib fracture. The PBD9 671 BP9 460 PBD8 679 BP8 480–481
sharp bone can penetrate the pleura and produce an air leak,
resulting in pneumothorax. Although pneumothorax can com- 4 B The trauma produced an air leak with interstitial em-
plicate rupture of a bulla in emphysema, this is more likely to physema. There could have been a pneumothorax as well,
occur in paraseptal emphysema or distal acinar emphysema but in this case air escaped and dissected into soft tissues. A
than in centrilobular emphysema with increased anteropos- process that increases intraparenchymal lung pressure and
terior diameter. Although pulmonary embolus with V/Q ruptures the lung, such as positive pressure ventilation, can
mismatch and pneumonia with patchy infiltrates are possible also lead to this complication. Interstitial emphysema looks
complications in hospitalized patients, they would not occur
this quickly. Pleural space fluid (hydrothorax) and edema are
C H A P T E R 1 5 The Lung 2 4 1
worse than it feels, and within days the air is resorbed. When neutrophils and macrophages that aggregate in alveolar cap-
the leak occurs centrally, the term mediastinal emphysema illaries and release toxic oxygen metabolites, cytokines, and
can be used. The term pulmonary interstitial emphysema (PIE) eicosanoids. Oxygen toxicity from high levels of inspired oxy-
describes this process in newborns, often with mechanical gen exacerbate DAD. The damage to the capillary endothelium
ventilation under positive pressure, and in the setting of re- allows leakage of protein-rich fluids. Eventually, the overlying
spiratory distress syndrome. Rupture of the stomach is most alveolar epithelium also is damaged. Aspiration of bacteria
likely to leak gastric acidic contents into the peritoneum to causes bronchopneumonia. ARDS and disseminated intravas-
produce peritonitis, and be recognized by free air under the cular coagulation (DIC) together can complicate septic shock,
diaphragm on radiographs. Blood in the pleural space is but DIC is not the cause of ARDS. Release of fibrogenic cyto-
called hemothorax; within soft tissues blood can form a hema- kines is an important cause of chronic diffuse pulmonary fibro-
toma. Leakage of lymph is rare, because the lymphatics have sis. Reduced surfactant production causes respiratory distress
little or no pressure within them; blockage of the thoracic duct syndrome with hyaline membrane disease in newborns.
may produce a chylothorax. Pus in the pleural space is called
empyema, and typically complicates an existing pneumonia. PBD9 672–674 BP9 461–463 PBD8 680–682 BP8 481–483
PBD9 678 BP9 460 PBD8 687 BP8 488 8 E The patient’s findings are predominantly those of an
obstructive lung disease—emphysema—with a centrilobular
5 D He has left-sided heart failure with pulmonary edema pattern of predominantly upper lobe involvement. Smoking
and congestion. His reduced cardiac output leads to dimin- is a major cause of this disease. The subtle but long-term in-
ished renal blood flow that stimulates the renin-angiotensin flammation that can accompany smoking leads to increased
mechanism to retain salt and water to increase plasma vol- neutrophil and macrophage elaboration of elastase that is
ume. He has prerenal azotemia with a high BUN-to-creatinine not sufficiently inhibited by the antiprotease action of α1-
ratio and low fractional excretion of sodium. The other op- antitrypsin. This results in a loss of lung tissue, not fibrogen-
tions do not explain his pulmonary edema. An aldosterone- esis, over decades. Fibrogenesis is typical of restrictive lung
secreting adrenal adenoma (Conn syndrome) would increase diseases, such as pneumoconioses, that follow inhalation of
aldosterone, but decrease the plasma renin. In chronic adrenal dusts. Abnormal chloride ion transport is a feature of cystic
failure (Addison disease), there should be hyperkalemia and fibrosis, which leads to widespread bronchiectasis. Dynein
hypoglycemia accompanying hyponatremia. Chronic glomer- arms are absent or abnormal in Kartagener syndrome, which
ulonephritis with chronic renal failure would be associated leads to bronchiectasis. α1-Antitrypsin deficiency is uncom-
with a BUN-to-creatinine ratio around 10:1. Pulmonary fibro- mon and leads to a panlobular pattern of emphysema. Macro-
sis would lead to cor pulmonale and a prominent right heart phage recruitment and activation by interferon-γ released from
border with features of right-sided congestive heart failure. T cells is a feature of chronic inflammatory conditions and
The syndrome of inappropriate antidiuretic hormone (ADH) pneumoconioses.
is a paraneoplastic syndrome that can occur with pulmonary
small cell carcinomas, and secretion of antidiuretic hormone PBD9 674–677 BP9 463–466 PBD8 684–686 BP8 485
(SIADH) would increase ADH and cause more severe hypo-
natremia, but would not have a major effect on the renin-an- 9 E Distal acinar (paraseptal) emphysema is localized,
giotensin mechanism, and sodium excretion would be higher. beneath pleura typically in an upper lung lobe, and may
o ccur in an area of fibrosis or scar formation. Although the
PBD9 671–672 BP9 460 PBD8 112–113 BP8 81–83 lesions are usually less than 2 cm in diameter, they are prone
to rupture spontaneously or with minor trauma, leading to
6 A She has acute lung injury with noncardiogenic pul- pneumothorax. They can be a cause for spontaneous pneu-
monary edema and development of diffuse alveolar damage mothorax in young adults. A “ball valve” effect can lead to
(DAD), clinically known as acute respiratory distress syndrome air trapping in pleura, producing tension pneumothorax, as
(ARDS). Inciting sepsis, trauma, or other forms of lung injury in this case. Centriacinar emphysema arises in respiratory
leads to a vicious cycle of inflammation with ongoing dam- bronchioles and is seen in smokers. Panacinar (panlobular)
age, mainly through the action of neutrophils. Plexiform le- emphysema involves most of the lung lobule and can be
sions are characteristic for pulmonary hypertension. Though seen in all lobes; α1-antitrypsin deficiency is the most likely
ARDS may eventually proceed to fibrosis, most patients do antecedent. Asthma results from bronchoconstriction with
not survive that long. Lymphocytic infiltrates may be seen air trapping, but is not likely to be complicated by pneu-
with infections such as viral pneumonias or immune-medi- mothorax. Bronchiectasis results from inflammation with
ated lung diseases. Destruction of respiratory bronchioles is a destruction of bronchi; hemoptysis is the most likely com-
feature of centrilobular emphysema. plication, not pneumothorax. Chronic bronchitis is unlikely
to produce a bronchopleural fistula with pneumothorax.
PBD9 672–674 BP9 461–463 PBD8 680–682 BP8 481–483
PBD9 675–676 BP9 464 PBD8 684 BP8 485–486
7 C This clinical and morphologic picture is that of acute
lung injury (ALI), which, when severe, leads to acute respira- 1 0 A These findings point to an obstructive lung disease,
tory distress syndrome (ARDS). ARDS is characterized by the such as emphysema, which occurs with airway narrowing
pathologic finding of diffuse alveolar damage (DAD), which is and loss of elastic recoil. It has led to compensated respiratory
initiated in most cases by injury to capillary endothelium, with acidosis in this man. Chronic pulmonary embolism does not
2 4 2 U N I T I I Diseases of Organ Systems
affect FVC because the airways are not affected, but there is 14 D Chronic bronchitis can be complicated by pulmo-
a ventilation-perfusion mismatch. Diffuse alveolar damage is nary hypertension and cor pulmonale. There are few char-
an acute restrictive lung disease. Nonatopic asthma can oc- acteristic microscopic features of chronic bronchitis, so it
cur at his age, but asthma is episodic and unlikely to cause is mainly defined clinically by the presence of a persistent
permanant loss of distal airspaces. Sarcoidosis is a form of cough with sputum production for at least 3 months in at
chronic restrictive lung disease. Pneumoconioses such as sili- least 2 consecutive years. Chronic bronchitis does not lead to
cosis produce a restrictive pattern of lung disease with all lung diffuse pulmonary fibrosis. Granulomatous disease is more
volumes decreased, low FVC, and normal FEV1/FVC ratio. typical of sarcoidosis or mycobacterial infection. Lymphan-
gitic metastases may fill lymphatic spaces and produce a
PBD9 674–677 BP9 463–466 PBD8 686–687 BP8 484–486 reticulonodular pattern on a chest radiograph, but patients
tend not to live long with such advanced cancer. Increased
11 E The extensive pulmonary involvement with eosinophils are characteristic of bronchial asthma, which is
increased lucency in all lung fields and increased anterior- an episodic disease unlikely to cause cor pulmonale.
posterior diameter is consistent with emphysema. The pan-
lobular form, which can be worse in the lower lobes, can be PBD9 678–679 BP9 467 PBD8 687–688 BP8 488–489
due to a decrease in α1-antitrypsin, which is the major cir-
culating antielastase. This deficiency is an inherited disease, 1 5 E Atopic asthma is a type I hypersensitivity reaction in
typically with the PiZZ genotype; liver disease may also oc- which there are presensitized, IgE-coated mast cells in mu-
cur. Individuals with atopy are more likely to develop asth- cosal surfaces and submucosa of airways. Contact with an
ma, which has transient air trapping, not emphysema. The allergen results in degranulation of the mast cells, with both
CFTR gene mutations lead to cystic fibrosis and widespread immediate release (minutes) of mediators such as histamine
pulmonary bronchiectasis, starting in childhood. Smoking to promote bronchoconstriction, and delayed release (an hour
increases inflammation with neutrophils releasing proteases, or more) of leukotrienes and prostaglandins via the arachi-
mainly in upper lobes, producing the centriacinar pattern of donic acid pathway; these attract leukocytes, particularly
emphysema over decades. Prior infection with tuberculosis eosinophils, and promote bronchoconstriction. The character-
may result in upper lobe cavitation, not emphysema. istic histologic changes in the bronchi, including remodeling
of airways and smooth muscle hyperplasia, result from the
PBD9 675–676 BP9 464 PBD8 684 BP8 485 episodes of inflammation. Dilation of the respiratory bronchi-
ole is a feature of centrilobular emphysema. Bronchial dilation
1 2 C This patient’s disease meets the clinical definition of with inflammatory destruction is a feature of bronchiectasis.
chronic bronchitis. He has had persistent cough with sputum Hyaline membranes are seen with acute diffuse alveolar dam-
production for at least 3 months in 2 consecutive years. Chron- age. Neutrophilic exudates with consolidation are seen in
ic bronchitis is a disease of smokers and individuals living in pneumonic processes, typically from bacterial infections.
areas of poor air quality, which explains the chronic cough
with mucoid sputum production. This patient’s episodes of PBD9 679–682 BP9 468–470 PBD8 688–692 BP8 490–492
bronchoconstriction set off by viral infections suggest, how-
ever, a superimposed element of nonatopic asthma. Cor pul- 1 6 A Asthma, particularly extrinsic (atopic) asthma, is driven
monale leads to pleural effusions, not to bronchoconstriction. by a type I hypersensitivity response and is associated with an
Centrilobular emphysema and chronic bronchitis (both com- excessive TH2 and TH17 cell-mediated immune response. Ge-
plications of smoking) can overlap in clinical and pathologic netic factors are important in the pathogenesis of atopic asthma
findings, but significant bronchoconstriction is not a feature and linkage to cytokine genes that map on 5q are strongly as-
of emphysema. The panlobular emphysema of α1-antitrypsin sociated with development of asthma and other atopic allergies.
can be worsened by smoking, but there is no bronchoconstric- The Charcot-Leyden crystals represent the breakdown prod-
tion. Bronchiectasis results in airway dilation from destructive ucts of eosinophil granules. The Curschmann spirals represent
bronchial wall inflammation, but the onset of pulmonary dis- the whorls of sloughed surface epithelium within the abundant
ease with cystic fibrosis is typically in childhood. Hypersensi- mucin. The septated hyphae are Aspergillus organisms colo-
tivity pneumonitis is marked by features of a restrictive lung nizing the tracheobronchial tree (allergic bronchopulmonary
disease, sometimes with dyspnea, but without mucus produc- aspergillosis). Foreign body aspiration may result in inflamma-
tion, and is often episodic from intermittent antigen exposure. tion, but without eosinophils. Inorganic dust inhalation leads to
restrictive, not obstructive, lung disease. CFTR mutations with
PBD9 678–679 BP9 467 PBD8 687–688 BP8 488–489 cystic fibrosis lead to chronic widespread bronchiectasis. In-
flammation with eosinophils is not a significant component of
1 3 D Centrilobular emphysema results from damage to emphysema related to α1-antitrypsin deficiency or to smoking.
the central part of the lung acinus, with dilation that pri-
marily affects the respiratory bronchioles. There is relative PBD9 679–682 BP9 468–470 PBD8 688–692 BP8 489–492
sparing of the distal alveolar ducts and alveolar sacs. Bron-
chi have cartilage that is not affected by emphysema. In 1 7 C The early, acute phase of bronchial asthma is triggered
panacinar emphysema, the lung lobule is involved from the by release of chemical mediators, whereas the late phase is
respiratory bronchiole to the terminal alveoli. In paraseptal mediated by recruited inflammatory cells and the Th2 cyto-
emphysema, the distal acinus is involved. kines they release. Acute asthmatic episodes respond best to
inhaled β-adrenergic agonists. Histamine released from mast
PBD9 675–676 BP9 464–465 PBD8 684 BP8 485–486 cells acts during the early acute phase of type I hypersensitivity
C H A P T E R 1 5 The Lung 2 4 3
reactions, but antihistaminic agents are not useful for treating is an anti-inflammatory agent that is used to treat immune-
recurrent bouts of asthma. Th2 cytokines play an important mediated diseases.
role in recurrent asthma and antagonists of these, in particular
IL-13 and IL-4, are in development. It is not clear if any one PBD9 680 BP9 470 PBD8 689 BP8 492
of the Th2 cytokines alone mediates recurrent bronchospasm.
Among the early to late phase mediators, the leukotrienes C4, 2 1 D He has Kartagener syndrome (sinusitis, bronchiec-
D4, and E4 promote intense bronchoconstriction and mucin tasis, and situs inversus associated with ciliary dyskinesia).
production. Montelukast is an agent that binds to cysteinyl There is an abnormality of ciliary dynein arms that dimin-
leukotriene (CysLT) receptors on mast cells and eosinophils to ishes the mucociliary function of the respiratory epithelium,
block the lipoxygenase pathway of arachidonic acid metabo- predisposing to recurrent and chronic infections of both up-
lism, which generates the leukotrienes. Prostaglandin D2 also is per and lower respiratory tract. Bronchiectasis is ongoing de-
a bronchoconstrictor, but its role is less well defined than that struction and dilation of bronchi with infection and airway
of leukotrienes. obstruction. α1-Antitrypsin deficiency leads to panlobular
emphysema, mainly of lower lobes, and the upper respira-
PBD9 679–682 BP9 468–470 PBD8 689–690 BP8 491 tory tract is not involved. Atopy may be associated with nasal
polyps, but leads to asthma, not bronchiectasis. Cystic fibrosis
18 B This history is typical of nonatopic, or intrinsic, asth- with CFTR gene mutations involving chloride ion channels
ma. There is no family history of asthma, no eosinophilia, can lead to widespread bronchiectasis, but generally not up-
and a normal serum IgE level. The fundamental abnormal- per airway problems, and not situs inversus. HIV infection is
ity in such cases is bronchial hyperresponsiveness (i.e., the marked by opportunistic infections with progression to AIDS,
threshold of bronchial spasm is intrinsically low). When but usually without bronchiectasis, and no situs inversus.
airway inflammation occurs after viral infections, the bron-
chial smooth muscle spasms, and an asthmatic attack occurs. PBD9 683–684 BP9 471 PBD8 692 BP8 493
Such bronchial hyperreactivity also may be triggered by in-
halation of air pollutants, such as ozone, sulfur dioxide, and 22 D Bronchiectasis is a chronic obstructive airway dis-
nitrogen dioxides. Even exercise and cold air may act as a ease from irreversible dilation of bronchi that results from
trigger. Accumulation of neutrophils is typical of bacterial inflammation and destruction of bronchial walls after pro-
pneumonia, which could follow viral infection, but lead to longed infections or obstruction. Serious bouts of pneumonia
lung consolidation. Bronchopulmonary aspergillosis refers can predispose to bronchiectasis. Congenital chondromala-
to colonization of asthmatic airways by Aspergillus, which is cia weakening the bronchial wall is rare. Bronchial mucosal
followed by development of additional IgE antibodies. Se- damage by eosinophils occurs in bronchial asthma. It does
cretion of interleukin (IL)-4 and IL-5 by type 2 helper T cells not cause destruction of the bronchial wall. Bronchioloalveo-
also occurs in cases of allergic asthma. lar carcinoma may mimic an infiltrative pneumonia because
of its lepidic pattern of spread, but it mainly produces a mass
PBD9 67–682 BP9 468–470 PBD8 688 BP8 490 effect, and it does not start in childhood. Unopposed action
of elastases damages the elastic tissue of alveoli, giving rise
1 9 E The TH2 helper lymphocyte response drives cytokine to emphysema.
production, such as IL-4, IL-5, and IL-13, that promotes eo-
sinophil infiltration and IgE production by mast cells. This PBD9 683–684 BP9 471–472 PBD8 692–693 BP8 493
allergic response potentiates inflammation, which promotes
the airway remodeling that facilitates additional airway re- 2 3 D The pulmonary function data suggest a restrictive
activity and asthmatic episodes. The TH1 response drives lung disease process. The progressive pulmonary interstitial
granulomatous inflammation. TH17 lymphocytes aid in in- fibrosis of a restrictive lung disease such as a pneumoco-
flammatory responses to infectious agents, but may play a niosis can eventually lead to dilation of remaining residual
role in autoimmunity. B lymphocytes produce antibodies, proximal airspaces, giving a honeycomb appearance. The
but mainly via the action of T helper cells. Cytotoxic lympho- loss of lung tissue with emphysema also leads to airspace
cytes are primarily directed at intracellular infectious agents. dilation, but without alveolar wall fibrogenesis. Eosinophilic
NK cells assist in fighting infectious agents. infiltrates suggest atopic asthma, an episodic disease with-
out fibrogenesis. The increase in mucous glands with chronic
PBD9 680–682 BP9 468–469 PBD8 689–691 BP8 489–491 bronchitis leads to copious sputum production, but not fi-
brogenesis. Hyaline membranes, edema, inflammation, and
2 0 B Drug-induced asthma is most likely to occur in older focal necrosis are features of diffuse alveolar damage (acute
patients who develop increased sensitivity to a drug. Aspi- respiratory distress syndrome) in the acute phase; if patients
rin (acetylsalicylic acid) blocks the cyclooxygenase pathway survive for weeks, diffuse alveolar damage may resolve to
of arachidonic acid metabolism but not the lipoxygenase honeycomb change.
pathway that potentiates bronchoconstriction. NSAIDs may
have the same effect as aspirin. Angiotensin-converting en- PBD9 684–686 BP9 472 PBD8 696–697 BP8 483–484
zyme (ACE) inhibitors may also induce asthmalike episodes.
Acetaminophen is an analgesic that can be substituted for 24 C The cause of many slowly progressive cases of re-
aspirin and is unlikely to provoke asthmatic attacks. Gaba- strictive lung disease is unknown, and the frustrated but
pentin and morphine act centrally as analgesics. Prednisone empathetic health care provider can only say, “I am sorry,
2 4 4 U N I T I I Diseases of Organ Systems
but there is nothing more that we can do.” These cases idiopathic condition in which there are gelatinous alveolar
must be distinguished from cases with identifiable causes, proteinaceous exudates.
such as infection, collagen vascular disease, drug use, and
pneumoconioses. Idiopathic pulmonary fibrosis leads to PBD9 687 BP9 473–474 PBD8 696, 720 BP8 496
progressive restrictive lung disease. An unknown antigen
incites the TH2 inflammatory process with activated macro- 2 8 C Silica crystals incite a fibrogenic response after in-
phage release of cytokines such as fibroblast growth factor halation and ingestion by pulmonary macrophages. The
and TGF-β1. TGF-β1 down-regulates telomerase activity greater the exposure to silica dust and the longer the time
and leads to epithelial cell apoptosis. TGF-β1 diminishes of exposure, the greater is the lung injury. Silica is a ma-
caveolin-1, a protein that inhibits fibrosis. Goodpasture jor component of the earth’s crust, including sand, which
syndrome is a form of type II hypersensitivity character- contains the mineral quartz. Mining, manufacturing, farm-
ized by diffuse pulmonary hemorrhage superimposed ing, and construction/renovation activities generate small
upon normal lung. Hypersensitivity pneumonitis may silica crystals that can be inhaled, and their buoyancy al-
have an element of type IV hypersensitivity with some fi- lows them to be carried to alveoli. There, they are ingested
brosis, but usually not as severe or rapid as in this case. by macrophages, which secrete cytokines that recruit other
Sarcoidosis is marked by granulomatous inflammation. In inflammatory cells and promote fibrogenesis. Carbon mon-
this case, scleroderma is less likely because of the negative oxide readily crosses the alveolar walls and binds avidly to
serologic test result. hemoglobin, but does not injure the lung directly. Ozone,
a component of smog, has no obvious pathologic effects.
PBD9 685–687 BP9 472–473 PBD8 694–695 BP8 494–495 Tobacco smoke leads mainly to loss of lung tissue and em-
physema, not to fibrosis. Particulate matter such as wood
25 E The inflammatory response to lung injury may de- dust is mainly screened out by the mucociliary apparatus
termine the nature and extent of the pulmonary disease. of the upper airways, but may invoke bronchoconstriction.
The cytokine TGF-β may modulate the mesenchymal cell
response to lung injury. Reduced TGF-β signaling may lead PBD9 688, 690 BP9 474–476 PBD8 698–699 BP8 498–499
to an inadequate repair response, with loss of lung paren-
chyma that characterizes emphysema. The PiZZ genotype 29 C Coal worker’s pneumoconiosis (CWP) is now less
of α1-antitrypsin deficiency puts persons, especially smokers common because of workplace safeguards in mining. Coal
with greater tobacco use, at increased risk for panlobular em- dust is relatively inert, so that large amounts must be inhaled
physema. BMPR2 is associated with development of primary before a fibrogenic response occurs, but the response contin-
pulmonary hypertension. Mutations in the CFTR gene are ues over many years. The other listed substances are more
associated with development of cystic fibrosis. Mutations in reactive. Asbestos produces ferruginous bodies. Chronic be-
GM-CSF are related to development of pulmonary alveolar rylliosis tends to be associated with sarcoidlike granulomas.
proteinosis. Iron produces siderosis with fibrosis. Sulfur dioxide is a gas
that contributes to obstructive lung diseases, particularly
PBD9 686–687 BP9 473 PBD8 494–495 BP8 494–495 chronic bronchitis and asthma.
2 6 E Nonspecific interstitial pneumonia has both cellular PBD9 689 BP9 474–476 PBD8 697–698 BP8 497–498
and fibrosing patterns, but the former has a better prognosis.
Some patients have an underlying connective tissue disease. 30 B The ferruginous bodies shown in the figure are
Desquamative interstitial pneumonitis (DIP) is smoking- long, thin crystals of asbestos that have become encrusted
related. Hypersensitivity pneumonitis most often relates to with iron and calcium. The inflammatory reaction incit-
episodic inhaled allergens and rarely progresses to marked ed by these crystals promotes fibrogenesis and resultant
interstitial disease. Idiopathic pulmonary fibrosis tends to pneumoconiosis. Anthracosis is a benign process seen in
have a more rapid course and involve more of the lungs. city dwellers as a consequence of inhaled carbonaceous
Nonatopic asthma is typically episodic and rarely progresses dust. Chronic berylliosis is marked by noncaseating gran-
to extensive interstitial disease. ulomas. Calcium deposition may rarely occur along alveo-
lar walls when the serum calcium level is very high (meta-
PBD9 686–687 BP9 472–473 PBD8 695 BP8 495–496 static calcification). Silica crystals are not covered by iron
and tend to result in formation of fibrous nodules (silicotic
27 B Bronchiolitis obliterans is a feature of cryptogenic nodules).
organizing pneumonia, an uncommon, nonspecific reac-
tion to a lung injury, such as an infection or toxic exposure. PBD9 690–692 BP9 477–478 PBD8 700 BP8 499–500
Bronchiectasis involves ongoing inflammatory destruction
with dilation of bronchi not reversed by corticosteroids. 3 1 C Silicotic nodules form when the silica crystals ingested
Desquamative interstitial pneumonitis (DIP) is an uncom- by macrophages elicit a fibrogenic response as cytokines, such
mon smoking-related interstitial disease in which monocytes as tumor necrosis factor, are released. The nodules may be-
gather to form intra-alveolar macrophages; DIP is not related come confluent with progressive massive fibrosis. Pneumoco-
to idiopathic pulmonary fibrosis. Hypersensitivity pneumo- nioses such as silicosis lead to restrictive lung disease. Cigarette
nitis is a type III (and type IV) hypersensitivity response to smoke contributes to loss of lung parenchyma with emphyse-
an inhaled allergen. Pulmonary alveolar proteinosis is a rare ma. Mold spores tend to elicit a hypersensitivity pneumonitis
C H A P T E R 1 5 The Lung 2 4 5
that rarely goes on to extensive restrictive lung disease. Sulfur 35 C Farmer’s lung is a form of hypersensitivity pneumo-
dioxide in polluted air tends to drive chronic obstructive lung nitis caused by inhalation of actinomycete spores in moldy
disease. Wood dust tends to elicit an asthmatic response. hay. These spores contain the antigen that incites the hyper-
sensitivity reaction. Because type III (early) and type IV im-
PBD9 690 BP9 476 PBD8 698–699 BP8 498–499 mune hypersensitivity reactions are involved, granuloma
formation can occur. The disease abates when the patient is
32 F She has a restrictive lung disease; the figure shows no longer exposed to the antigen. Chronic exposure can lead
hilar adenopathy and a reticulonodular pattern of infiltrates to more extensive interstitial lung disease. Antibodies direct-
characteristic of sarcoid. The blood gas values show mild hy- ed against pulmonary basement membrane are a feature of
poxemia with a compensated respiratory alkalosis. Because Goodpasture syndrome, which mainly produces pulmonary
there is no obstructive disease, the CO2 can be normal or hemorrhage. Silicosis can produce a restrictive lung disease
low from increased respirations to compensate for the diffu- with fibrosis, but there are nodules of fibrosis that develop
sion block (with low DLCO). α1-Antitrypsin deficiency and over years with minimal inflammation. Pulmonary tuber-
chronic bronchitis lead to obstructive lung disease with in- culosis can produce granulomas, but the pattern would be
creased total lung capacity and diminished FEV1 and respi- miliary, and it is unlikely that it would continue for 15 years.
ratory acidosis. Chronic bronchitis is defined by prolonged Pneumoconioses with exposure to dusts such as silica can
sputum production. Diffuse alveolar damage is an acute re- produce interstitial fibrosis over many years, and the risk
strictive lung disease from a severe underlying injury, such of neoplasia is increased slightly for silicosis and greatly for
as sepsis. Goodpasture syndrome results in pulmonary hem- asbestosis.
orrhage with hemoptysis. Asthma is an acute obstructive
lung disease with dyspnea and wheezing. PBD9 694–695 BP9 480–481 PBD8 703 BP8 503
PBD9 693–694 BP9 478–480 PBD8 701–703 BP8 501–502 36 A Hypersensitivity pneumonitis has acute symptoms
that occur soon after exposure to an antigen, often actino-
3 3 C This patient has an occupational risk of asbestos ex- mycetes or fungi (molds) growing in contaminated HVAC
posure. The inhaled asbestos fibers become encrusted with systems (air conditioner or ventilation ducts). The symptoms
iron and appear as the characteristic ferruginous bodies with improve when the patient leaves the environment where the
iron stain. The firm, tan mass encasing the pleura is most antigen is located. The pulmonary pathologic changes are
likely a malignant mesothelioma. Asbestosis more common- usually minimal, with interstitial mononuclear infiltrates. It
ly gives rise to pleural fibrosis and interstitial lung disease, is mainly a type III hypersensitivity reaction, but with more
similar to other pneumoconioses. This is seen grossly as a chronic exposure to the antigen, there may be a component
dense pleural plaque, which often is calcified. Asbestosis can of type IV hypersensitivity with granulomatous inflammation
give rise to bronchogenic carcinoma, especially in smokers. and fibrosis. Attachment of antibody to basement membrane
Fluffy infiltrates suggest an infectious process. Upper lobe occurs in Goodpasture syndrome. Mycolic acid is a compo-
cavitation suggests secondary tuberculosis. An endobron- nent of the cell wall of mycobacteria, and infections with these
chial mass could be a carcinoid tumor, which is not related to organisms are chronic, not episodic. Prostaglandins are pro-
asbestosis. The pleural mass likely leads to obliteration of the duced by the cyclooxygenase pathway of arachidonic acid
pleural space, with no effusion. metabolism during acute inflammation, and they mediate
pain and vasodilation. Histamine release is characteristic of a
PBD9 690–692 BP9 477–478 PBD8 699–701 BP8 499–500 type I hypersensitivity reaction that more typically occurs in
allergic disease. A toxic injury is more typical of inhalation of a
34 A The clinical and morphologic features strongly toxic gas, such as sulfur dioxide (so-called silo filler’s disease).
suggest sarcoidosis. This granulomatous disease has an
unknown cause, but the presence of granulomas and acti- PBD9 694–695 BP9 480–481 PBD8 703–704 BP8 503
vated T cells in the lungs indicates a delayed hypersensitiv-
ity response to some inhaled antigen. Lung involvement, 37 B He has desquamative interstitial pneumonitis (DIP),
occurring in about one third of cases, may be asymptomatic one form of smoking-related interstitial lung disease. Most
or may lead to restrictive lung disease. Sarcoidosis can in- cases abate with cessation of smoking and corticosteroid
volve multiple organs, particularly those of the mononuclear therapy. Atopy is classically related to asthma, an acute ob-
phagocyte system, especially lymph nodes. Diffuse alveolar structive pulmonary process. One form of primary ciliary
damage is an acute lung injury seen in acute respiratory dis- dyskinesia is Kartagener syndrome, which leads to bronchi-
tress syndrome. Hypersensitivity pneumonitis is an immune ectasis from ongoing inflammation with infection. Inhalation
complex disease that is triggered by inhaled allergens. This of mold spores produces farmer’s lung—hypersensitivity
form of lung disease is characterized by acute dyspneic epi- pneumonitis. Inhalation of silicates leads to pulmonary fibro-
sodes. The disease starts with type III hypersensitivity, but sis over years, but without large numbers of macrophages.
there can sometimes be granulomas in the lung, and lymph
node enlargement is not seen. Atypical mycobacteria cause PBD9 695–696 BP9 481 PBD8 704 BP8 481–482, 504
caseating granulomas, as does Mycobacterium tuberculosis.
Smoking causes chronic bronchitis and emphysema. 3 8 E The acquired form of pulmonary alveolar proteinosis
(PAP) is an uncommon condition of unknown etiology char-
PBD9 693–694 BP9 478–480 PBD8 701–703 BP8 501–502 acterized by autoantibodies against granulocyte-macrophage
2 4 6 U N I T I I Diseases of Organ Systems
colony-stimulating factor (GM-CSF). Ten percent of PAP cases upon lung parenchyma. There is no bronchoconstriction. With
are congenital secondary to mutations in the GM-CSF gene. such an acute course, there is not enough time for a hemor-
Both forms of PAP have impaired surfactant clearance by al- rhagic pulmonary infarction to occur. Edema is not a feature of
veolar macrophages, leading to accumulation of a gelatinous thromboembolism.
alveolar exudate. α1-Antitrypsin deficiency leads to panlobu-
lar emphysema with hyperlucent lungs on radiographs. CFTR PBD9 697–699 BP9 482–483 PBD8 706–707 BP8 504–506
gene mutations lead to cystic fibrosis and widespread bron-
chiectasis. Anti–DNA topoisomerase I antibodies are seen in 42 D Over half of persons with chronic pulmonary throm-
diffuse scleroderma, which produces pulmonary interstitial boembolism with pulmonary hypertension do not have a
fibrosis. Anti–glomerular basement membrane antibody is history of recurrent pulmonary embolism. Rather than one
present in Goodpasture syndrome with extensive alveolar large life-threatening embolus, chronic thromboembolism
hemorrhage. Neutrophilic myeloperoxidase is a form of anti– occurs from multiple smaller emboli that reduce the pulmo-
neutrophil cytoplasmic autoantibody seen in ANCA-associat- nary vascular bed and increase pulmonary pressures, lead-
ed vasculitis. ing to cor pulmonale. Recanalization of thrombi leads to
narrow channels causing the bruits. Antiphospholipid anti-
PBD9 696–697 PBD8 705 bodies pose a risk for thrombosis. The risk factors for system-
ic arterial atherosclerosis are not operative in the pulmonary
3 9 D The CT scan shows large filling defects with de- arterial tree, and pulmonary atherosclerosis is a consequence
creased attenuation within large pulmonary arteries. This of pulmonary hypertension, not a cause of it. Pneumonitis
lesion is typical of pulmonary thromboembolism that affects with parenchymal inflammation reduces ventilation more
patients who are immobilized in the hospital, such as pa- than perfusion. Sarcoidosis is an idiopathic granulomatous
tients with congestive heart failure. The source of the emboli disease that mainly affects the pulmonary parenchyma.
is usually thrombi within deep pelvic or leg veins affected ANCA-associated vasculitis of the pulmonary arterial tree
by phlebothrombosis. Patients with underlying cardiac or may produce vascular occlusion, but there is usually paren-
respiratory diseases that compromise pulmonary circulation chymal disease as well, along with multisystem involvement.
are at greater risk of infarction if thromboembolism does oc-
cur. Thromboembolism is not a complication of smoking in PBD9 697–699 BP9 482–483 PBD8 706–707 BP8 504–506
patients with emphysema or asthma. HIV infection increases
the risk of pulmonary infections, but not of thromboembo- 43 A This patient has findings associated with right and
lism. The small emboli from the small vegetations of nonbac- left heart failure. The left-to-right shunt produced by the atri-
terial thrombotic endocarditis are unlikely to produce such al septal defect leads to increased pulmonary arterial pres-
large filling defects, and most of them arise on the left side of sure, thickening of the pulmonary arteries, and increased
the heart. Vasculitis of the lung typically involves arterioles, pulmonary vascular resistance. Eventually, the shunt may
capillaries, or venules of insufficient size to produce a gross- reverse, which is known as the Eisenmenger complex. The
ly apparent filling defect in large arteries. Pneumoconioses pleural effusions are the result of right heart failure from
with restrictive lung disease produce pulmonary fibrosis, cor pulmonale. The chest radiograph findings here do not
but not a compromised vasculature or thromboembolism. include interstitial disease. Granulomatous inflammation
does not occur from increased pulmonary arterial pressure,
PBD9 697–699 BP9 482–483 PBD8 706 BP8 505 but extensive granulomatous inflammation, as with sarcoid-
osis, may lead to pulmonary hypertension. An infarction of
4 0 F The findings in this study suggest pulmonary thrombo- the lung can occur with pulmonary embolism. Pulmonary
embolism, and most pulmonary emboli are small and clinically interstitial fibrosis can be caused by diseases such as pneu-
silent. Dyspnea can occur with medium to large emboli. He- moconioses, collagen vascular diseases, and granulomatous
moptysis with pulmonary embolism is uncommon, although it diseases; interstitial lung disease can lead to pulmonary hy-
may occur when a hemorrhagic infarction results from throm- pertension. Pulmonary necrotizing vasculitis may be seen
boembolism. Cor pulmonale can result from repeated emboli- with immunologically mediated diseases, such as ANCA-
zation with reduction in the pulmonary vascular bed, leading associated vasculitis.
to heart failure and arrhythmias with palpitations, but this is
not common. Thromboembolism with infarction based upon PBD9 699–700 BP9 484–485 PBD8 707 BP8 506–507
the pleura may lead to pleuritic pain. Sudden death may occur
with large emboli that occlude the main pulmonary arteries be- 44 B The finding of pulmonary hypertension in a young
fore any other changes can occur. Orthopnea from fluid-filling individual without any known pulmonary or cardiac dis-
airspaces most likely accompanies heart failure. ease is typical for primary pulmonary hypertension. The in-
creased pulmonary arterial pressure leads to hypertrophy of
PBD9 697–699 BP9 482–483 PBD8 706–707 BP8 504–506 the right side of the heart. The large pulmonary arteries show
atherosclerosis; the arterioles show plexogenic arteriopathy
4 1 E The figure shows a saddle pulmonary thromboem- with a tuft of capillary formations producing a network, or
bolus in the opened main pulmonary arteries. Sudden death web, that spans the lumens of dilated thin-walled arteries.
occurs from hypoxemia or from acute cor pulmonale with BMPR2, a cell surface protein belonging to the TGF-β recep-
right-sided heart failure. Because the airways are not ob- tor superfamily, causes inhibition of vascular smooth muscle
structed, the lungs do not collapse, and there is no mass effect cell proliferation and favors apoptosis. In the absence of
C H A P T E R 1 5 The Lung 2 4 7
BMPR2 signaling, smooth muscle proliferation occurs, and produce squamous metaplasia, which most typically occurs
pulmonary hypertension ensues. Inactivating germline mu- in response to chronic irritation, as from cigarette smoke.
tations in the BMPR2 gene are found in 50% of the familial The subglottic tracheal region, where the cuff of the endo-
(primary) cases of pulmonary hypertension and in 26% of tracheal tube is located, can become eroded, but this is more
sporadic cases. None of the other molecules listed regulate likely to occur when intubation is prolonged for weeks.
pulmonary arterial wall structure. Endothelial nitric oxide
controls vascular caliber. B-type natriuretic peptide and PBD9 702, 706 BP9 486–487 PBD8 710 BP8 510
renin regulate sodium and water homeostasis, plasma vol-
ume, and systemic arterial pressure. Mutation in the gene for 48 F The productive cough suggests an alveolar exudate
fibrillin-1 (FBN1) occurs in Marfan syndrome. Lysyl hydrox- with neutrophils, and the course is compatible with an acute
ylase is required for cross-linking collagen, and its loss gives infection. Bacterial organisms should be suspected. Pneumo-
rise to one form of Ehlers-Danlos syndrome. coccus is the most likely agent to be cultured in individuals
acquiring pneumonia outside of the hospital, and particular-
PBD9 699–700 BP9 484–485 PBD8 707–709 BP8 506–507 ly when a lobar pneumonic pattern is present, as in this case.
The primary atypical pneumonia of Mycoplasma does not
4 5 B Goodpasture syndrome leads to renal and pulmo- usually produce purulent sputum, unless there is a second-
nary lesions produced by an antibody directed against an ary bacterial infection, which is a common complication of
antigen common to the basement membrane in glomerulus viral and Mycoplasma pneumonias. Cryptococcal and myco-
and alveolus. This leads to a type II hypersensitivity reac- bacterial infections typically produce granulomatous disease.
tion. The anti–DNA topoisomerase I antibody is a marker for Nocardiosis also is seen in immunocompromised patients
scleroderma. Antimitochondrial antibody is associated with and produces chronic abscessing inflammation. Pneumocystis
primary biliary cirrhosis. C-ANCA and P-ANCA are best pneumonia is seen in immunocompromised patients and is
known as markers for various forms of systemic vasculitis. unlikely to produce a lobar pattern of infection.
ANA is used as a general screening test for various autoim-
mune conditions, typically collagen vascular diseases such PBD9 702–704 BP9 487–489 PBD8 711–714 BP8 509–511
as systemic lupus erythematosus.
4 9 C The short time course and acute inflammatory
PBD9 701 BP9 485 PBD8 709–710 BP8 507–508 response are consistent with bacterial pneumonitis. Mo-
raxella is the only bacterial organism listed and is in the
4 6 D Polyangiitis with granulomatosis, a form of ANCA- differential diagnosis of both upper and lower respiratory
associated vasculitis, may affect multiple organs, but the lung infections, particularly in persons with chronic obstructive
and kidney are most often involved. The C-ANCA test (PR3) pulmonary disease (COPD), such as this woman. Morax-
result is often positive in granulomatosis with polyangiitis, ella is an aerobic gram-negative diplococcus that is oxidase
whereas a positive P-ANCA (MPO) result suggests micro- positive. Histoplasmosis is typically a granulomatous dis-
scopic polyangiitis. Renal and pulmonary disease may be ease that develops over weeks. Influenza A viral infection
present in Goodpasture syndrome; there may be a positive is interstitial, without neutrophilia. M. kansasii produces
result for anti–glomerular basement membrane antibody, but pulmonary granulomatous disease similar to tuberculosis.
no C-ANCA or P-ANCA positivity. Of the collagen vascular Pneumocystis pneumonia is most often seen in immuno-
diseases, systemic sclerosis is more likely to produce signifi- compromised persons.
cant pulmonary disease, but hemoptysis is not a prominent
feature, and the C-ANCA result is unlikely to be positive. In PBD9 703 BP9 487–489 PBD8 712 BP8 512
systemic lupus erythematosus, renal disease is far more likely
than pulmonary disease, and C-ANCA or P-ANCA positivity 5 0 E A lung abscess often results from aspiration, which
is not expected, but anti-Smith and anti-dsDNA are most spe- can occur in individuals with a depressed cough reflex or in
cific for SLE. Anti-GBM is a feature of Goodpasture syndrome neurologically impaired individuals (e.g., owing to acute al-
with extensive intra-alveolar hemorrhage. In hypersensitivity coholism, anesthesia, or Alzheimer disease). Aspiration into
pneumonitis, often the result of inhalation of thermophilic ac- the right lung and the lower lobe is more common because
tinomycetes, an initial type III hypersensitivity response is fol- the main bronchus to the left lung is more acutely angled.
lowed by a type IV response, and renal disease is not expected. Bacterial organisms are most likely to produce abscesses, and
the infection may be polymicrobial. The most common patho-
PBD9 507, 511, 701–702 BP9 485 PBD8 516–517, 709 BP8 508 gen is Staphylococcus aureus, but anaerobes such as Bacteroides,
Peptococcus, and Fusobacterium spp. also may be implicated.
47 A The anesthetic gases tend to reduce the ciliary func- These anaerobes normally are found in the oral cavity and
tion of the respiratory epithelium that lines the bronchi. The are readily aspirated. The purulent, liquefied center of the
mucociliary apparatus helps clear organisms and particu- abscess can produce the radiographic appearance of an air-
late matter that are inhaled into the respiratory tree. Mac- fluid level. Cytomegalovirus, Pneumocystis, and cryptococcal
rophage function is not significantly affected by anesthesia. infections are seen in immunocompromised individuals and
The levels of γ-globulins in serum are not reduced by the ef- do not typically form abscesses. Candida pneumonia is rare.
fects of anesthesia. The anesthetic gases and induction drugs Nocardial and actinomycotic infections often lead to chronic
do not typically result in marrow failure with neutropenia. abscesses without significant liquefaction and affect im-
The exposure to anesthetic gases is not prolonged enough to munocompromised individuals. Tuberculosis can produce
2 4 8 U N I T I I Diseases of Organ Systems
granulomatous lesions with central cavitation that may be infections of the lower respiratory tract are uncommon even
colonized by Aspergillus, although not over a few days. in immunocompromised persons. Cytomegalovirus is most
likely to involve the lungs of immune compromised persons.
PBD9 702, 708–709 BP9 488–489, 492 PBD8 716–717 BP8 515 H. influenzae is more likely to produce neutrophilic patchy
infiltrates with productive cough.
5 1 C This primary atypical pneumonia is caused by My-
coplasma pneumoniae, a cell wall–deficient organism that is PBD9 706–707 BP9 493–498 PBD8 367–372, 717 BP8 516–521
difficult to culture. Often, a diagnosis is made empirically.
The findings are similar to those of other viral infections, and 55 C Respiratory syncytial virus (RSV) pneumonia is most
serologic testing shows the specific organism. Legionella can common in children, and it can occur in epidemics. Viral,
produce an extensive pneumonia with neutrophilic alveolar chlamydial, and mycoplasmal pneumonias are most often
exudates, and the organisms are difficult to show—they may interstitial, without neutrophilic alveolar exudates. The di-
be revealed by Dieterle silver stain. Mycobacterium fortuitum agnosis is often presumptive because viral culture is techni-
is a rare infection that is most likely to be seen in very ill cally difficult and expensive, such as a PCR assay. Hyperinfla-
or immunocompromised individuals. Nocardiosis produces tion can accompany bronchoconstriction in asthma. Marked
chronic abscessing inflammation; it is seen mostly in im- lymphadenopathy is more characteristic of chronic processes,
munosuppressed individuals. Respiratory syncytial virus is such as granulomatous diseases or metastases. Lobar consoli-
typically an infection of early childhood. dation is more typical of a bacterial process, such as can be
seen in Streptococcus pneumoniae infection. Pleural effusions
PBD9 704 BP9 490 PBD8 714–715 BP8 513–514 can be seen in pulmonary inflammatory processes, but they
are most pronounced in heart failure. Cavitation is most likely
5 2 A Severe acute respiratory syndrome is caused by a to complicate secondary tuberculosis in adults.
strain of coronavirus that is much more virulent than the
coronaviruses known to be associated with the common PBD9 705 BP9 491 PBD8 349, 714–715 BP8 511, 536
cold. Cytomegalovirus is seen in immunocompromised pa-
tients and often involves multiple organs. Ebola virus is viru- 5 6 D Nontuberculous mycobacterial infections such as
lent and does not cause specific respiratory findings. Herpes Mycobacterium avium-complex (MAC) are likely to become
simplex virus is a very rare cause of pneumonia, even in disseminated illnesses in immunocompromised persons. In
immunocompromised patients. Respiratory syncytial virus immunocompetent persons, such infections are more likely
causes acute respiratory illness in young children. to resemble tuberculosis. The acid-fast MAC organisms pro-
liferate profusely in macrophages within the mononuclear
PBD9 707 BP9 491 PBD8 716 BP8 514 phagocyte system. Extensive and severe aspergillosis and
candidiasis are more likely to occur with profound neutrope-
53 B The antigenic drift of influenza viruses, by mutation nia, not lymphocytopenia. Legionella produces an extensive
with minor alteration of either their hemagglutinin (H) or bacterial pneumonia, not disseminated disease. Nocardiosis
neuraminidase (N) genes, allows them to escape host anti- occurs in immunocompromised patients, and the organisms
bodies. A shift occurs with major change in H or N or both, as can be weakly acid-fast, but focal nodules or a chronic abs-
happened with H1N1 in this case. Cleavage of influenza viral cessing inflammatory response are more likely.
hemagglutinin by host proteases is essential for the virus to
enter cells. The less virulent influenza viruses are cleaved by PBD9 376–377 BP9 499 PBD8 372–373 BP8 523
proteases that are mainly localized to the lung and hence the
disease is limited to the lungs. H5N1 virus has much broader 5 7 A The figure shows pink, amorphous tissue at the
tissue tropism because its hemagglutinin can be cleaved by lower left, representing caseous necrosis. The rim of the
proteases present in many tissues. Host responses to flu virus, granuloma has epithelioid cells and Langhans giant cells.
such as a cytotoxic T-cell response or macrophage engulf- Caseating granulomatous inflammation is most typical of
ment, are not the major determinant of pathogenicity. Selec- Mycobacterium tuberculosis infection. Calcifications would
tive infection of CD4+ T cells is a propensity of HIV. Current- have helped to identify this mass as an old granuloma, not
ly avian flu cannot be spread from human to human—but likely to be a neoplasm. Necrotizing vasculitis is unlikely
should that happen there would be an avian flu pandemic. to produce a single nodule, and there can be hemoptysis.
A carcinoma may have central necrosis, not caseation, and
PBD9 346, 705–706 BP9 491 PBD8 715 BP8 514 there would be atypical, pleomorphic cells forming the
mass. A pulmonary infarct should have extensive hemor-
54 F Human metapneumovirus is second only to respira- rhage. A lung abscess would have an area of liquefactive
tory syncytial virus as a cause for pediatric lower respiratory necrosis filled with tissue debris and neutrophils.
infection, and the two are indistinguishable clinically. She
mainly has bronchiolitis. Like most viral infections, round PBD9 371–376 , 709 BP9 493–497 PBD8 367–372 BP8 516–519
cell infiltrates are interstitial, and those at greatest risk are the
very young, elderly, and immunocompromised. Group A 58 A This “coin lesion” on imaging of his lungs could be an
streptococcal infections typically produce pharyngitis. Per- infectious granuloma, a neoplasm, or a hamartoma. His fever
tussis is rare when childhood vaccinations are done; it causes suggests infection, and the CT finding of decreased central
whooping cough from upper airway involvement. Candida attenuation in the nodule suggests necrosis in a neoplasm
C H A P T E R 1 5 The Lung 2 4 9
or caseous necrosis in a granuloma. The lymphocytosis and 61 D The radiograph in the figure shows prominent up-
monocytosis are consistent with tuberculosis. Nonsmokers per lobe cavitation, typical of reactivation-reinfection tuber-
are unlikely to develop primary lung neoplasms, and adeno- culosis in adults. Candida is a rare cause of lung infection.
carcinoma is the most common in that setting. Smokers are Influenza viral infections have mainly interstitial mononu-
most likely to develop squamous cell carcinomas and small clear inflammation. Bacterial organisms such as Legionella
cell anaplastic carcinomas. Individuals who are immuno- are more likely to produce a widespread bronchopneumonia
compromised are most likely to develop fungal infections, with alveolar neutrophilic exudates. Mycoplasma infection
particularly with Aspergillus spp., which have branching sep- produces mainly interstitial mononuclear inflammation. No-
tate hyphae. Charcot-Leyden crystals form from eosinophil cardiosis of the lung appears mainly as chronic abscessing
granules in individuals with allergic asthma. Foreign body inflammation.
giant cells can be seen with lipid pneumonias. Gram stain is
most useful for determining which bacterial organisms may PBD9 374–376 BP9 496–498 PBD8 369–372 BP8 520–521
be present, and gram-negative bacilli such as the Entero-
bacteriaceae produce acute pneumonias and abscesses with 6 2 A There are several patterns of pulmonary involve-
neutrophilia. ment with Aspergillus spp. Immunocompromised patients
with neutropenia may develop invasive aspergillosis. Other
PBD9 374–376 BP9 498 PBD8 718, 730 BP8 522 patterns include allergic bronchopulmonary aspergillosis in
persons with asthma and an aspergilloma, or fungus ball,
59 C These findings represent the so-called Ghon (or colonizing a cavitary lesion of tuberculosis or bronchiectasis.
primary) complex, consisting of a small subpleural granu- Candidiasis may also develop in the setting of neutropenia,
loma with extensive hilar nodal caseating granulomas. The but less commonly causes extensive lung involvement, ap-
Ghon complex is a feature of primary tuberculosis, which pears as budding cells with pseudohyphae, and more likely
is most often a subclinical disease of younger individu- produces an oral, nasal, or pharyngeal infection. Cryptococ-
als. The interferon-γ release assay is positive when T lym- cosis can cause extensive pulmonary infections, particularly
phocytes are activated against Mycobacterium tuberculosis with loss of cell-mediated immunity, and the organisms have
antigens, and is negative in individuals who received BCG large mucoid capsules and exhibit narrow-based budding.
vaccination. Individuals who are immunocompromised, Moraxella is a bacterial organism most often causing sinus-
such as HIV-infected patients, do not mount a good granu- itis, otitis, and upper respiratory infections. Mucor a ppears as
lomatous response and have more extensive poorly formed broad, nonseptated hyphae and is most often a complication
granulomas, dissemination of tuberculosis, or both. Anticen- of diabetic ketoacidosis, with nasal involvement.
tromere antibody is characteristic of limited scleroderma,
which does not have significant pulmonary involvement, PBD9 388–389, 712 BP9 504 PBD8 384–385, 720 BP8 324, 527
in contrast to diffuse scleroderma. The rapid plasma reagin
test is used to diagnose syphilis, which does not have signifi- 6 3 C Within the airspace are multiple large cells with
cant pulmonary disease. Rheumatoid nodules may be seen prominent purple intranuclear inclusions, typical for CMV.
in rheumatoid arthritis; these can be subpleural, but patients Although CMV antibodies can be found in most immuno-
typically have arthritis. Patients with cystic fibrosis and an el- competent persons, the infection is subclinical. However,
evated sweat chloride level (more often elevated in children in immunocompromised persons, CMV infection can be a
than in adults) develop widespread bronchiectasis along severe and systemic infection, including marked interstitial
with infection by bacterial agents, particularly Pseudomonas pneumonitis. The other listed organisms are much smaller.
aeruginosa and Burkholderia cepacia. Candida is a rare cause for pneumonia, and this yeast appears
as budding cells and pseudohyphae. Cryptococcal organ-
PBD9 374–375 BP9 495 PBD8 370 BP8 519 isms exhibit narrow-based budding and thick mucoid cap-
sules. Klebsiella pneumoniae organisms are encapsulated, but
60 B Coccidioidomycosis is endemic to semiarid regions these bacteria are too small to be seen with H&E staining.
of the Americas. The species Coccidioides immitis is found Pneumocystis organisms are best seen with Gomori methena-
in the southwestern United States, and the nearly identi- mine silver stain and appear as round to cup-shaped cysts.
cal Coccidioides posadasii is found from Mexico to South
A merica. D imorphic fungal diseases may produce granulo- PBD9 359–360, 711 BP9 500–501 PBD8 353–355 BP8 323, 720
matous infection resembling tuberculosis. The miliary pat-
tern described in this patient occurs with a poor immune 6 4 C Although Pneumocystis jiroveci pneumonia can be
response. Blastomyces dermatitidis organisms are smaller seen with various acquired and congenital immunodeficient
than 10 microns and exhibit broad-based budding. His- states (mainly those affecting cell-mediated immunity), it is
toplasma capsulatum organisms are 2 to 4 microns and are most often associated with AIDS and is diagnostic of AIDS in
often found within phagocytic cells. Mycobacteria are acid- HIV-infected individuals. Persons with diabetes mellitus and
fast rod-shaped organisms only a micron across. Nocardia pulmonary emphysema are most prone to contract bacterial
o rganisms are long, filamentous bacteria that may be weakly infections. Patients with autoimmune diseases may have cy-
acid-fast. Paracoccidioides brasiliensis organisms can be 20 to topenias that predispose to infection, and if they are treat-
30 microns and exhibit multiple buds in a “captain’s wheel” ed with immunosuppressive drugs, various infections are
configuration. possible. Likewise, patients with sarcoidosis treated with cor-
ticosteroid therapy may have opportunistic infections. A pa-
PBD9 710–711 BP9 499–500 PBD8 719 BP8 523 tient with severe combined immunodeficiency is susceptible
2 5 0 U N I T I I Diseases of Organ Systems
to P. jiroveci pneumonia, but it is unlikely that without treat- 6 8 A Cancers that arise in nonsmokers are pathogenetical-
ment such a patient would have survived to age 40 years. ly distinct from those that occur in smokers. They may have
either EGFR mutations or KRAS mutations. Most are adeno-
PBD9 400, 711 BP9 501–502 PBD8 720 BP8 525–526 carcinomas. Twenty-five percent of lung cancers worldwide
occur in nonsmokers. Primary adenocarcinomas in the lung
65 G Of all lung cancers, squamous cell carcinoma is most tend to be small, peripheral masses that are amenable to sur-
likely to produce paraneoplastic hypercalcemia, and there gical excision and have a better overall prognosis than other
is a strong association with smoking. These tumors also can forms of lung cancer. Overall, far more metastatic adenocar-
undergo central necrosis—hence a cavity may form. Local- cinomas involve the lung than do primary adenocarcinomas.
ized squamous cell carcinomas, in contrast to small cell car- Bronchial carcinoids are uncommon endobronchial lesions.
cinomas, may be cured by surgery. Adenocarcinomas and Hamartomas are small, peripheral masses that contain be-
large cell carcinomas tend to produce peripheral masses and nign epithelial and connective tissue elements. Large cell
generally are less likely to be associated with paraneoplas- carcinomas are too poorly differentiated to be called adeno-
tic syndromes. Kaposi sarcoma involving visceral organs carcinomas or squamous cell carcinomas. The most common
is most often seen in association with AIDS, and it is often cancers in smokers are small cell anaplastic and squamous
multifocal. Renal cell carcinomas may be associated with cell carcinomas.
hypercalcemia, but metastases usually appear as multiple
masses (although of all metastatic tumors, renal cell carci- PBD9 714–716 BP9 505–506 PBD8 724–729 BP8 529–533
noma is most likely to produce solitary metastases). Non-
Hodgkin lymphomas generally do not have paraneoplastic 6 9 F Cushing syndrome is a paraneoplastic syndrome re-
effects; they are uncommon in the lung and are not associ- sulting from ectopic corticotrophin production (most often
ated with smoking. Small cell carcinomas are never localized from a pulmonary small cell carcinoma), which drives the
enough for curative surgery (they are usually detected at an adrenal cortices to produce excess cortisol. Small cell carci-
advanced stage), although they often produce various para- nomas are aggressive neuroendocrine tumors that tend to
neoplastic syndromes, but less likely hypercalcemia. metastasize early. Even when they appear to be small and
localized, they are not or will not remain so. Surgery is not an
PBD9 712–716 BP9 506, 510 PBD8 725–726 BP8 531–534 option for these patients. They are treated as if they have sys-
temic disease; some chemotherapy protocols afford benefit
6 6 A The long history and the weight loss suggest a chron- for 1 year or more, but cure is uncommon. Adenocarcinomas
ic, debilitating process. The radiograph shows multiple mass and large cell carcinomas tend to be peripheral neoplasms in
lesions. The focal nature of the lesions, with remaining pul- the lung, and they are less likely to produce a paraneoplastic
monary reserve capacity, means that measured lung func- syndrome. Bronchial carcinoids at the more benign end of the
tion remains normal. The most common neoplastic process neuroendocrine tumor spectrum tend to be small and are not
of lung is metastatic disease, because many primary sites likely to produce paraneoplastic effects; rarely, they produce
outside of lung can gain vascular access and spread hema- carcinoid syndrome. Non-Hodgkin lymphomas rarely occur
togenously, and lung has a rich capillary bed for tumor cell within the lung, are not associated with smoking, and do not
emboli to colonize. Immunohistochemical markers on this produce Cushing syndrome. Squamous cell carcinomas can
adenocarcinoma might help characterize the primary site, or be central and occur in smokers, but they are more likely to
they might not. Depending upon the markers, there might produce hypercalcemia as a paraneoplastic syndrome.
be specific antineoplastic therapies, or not. The lack of fe-
ver and any evidence for inflammation makes an infectious PBD9 713–715, 717, 719 BP9 509–510 PBD8 728 BP8 534
process unlikely. Necrotizing vasculitis is likely to produce
hemoptysis. Silicosis is unlikely without an environmental 70 A Adenocarcinoma in situ (AIS), formerly termed bron-
exposure in a job setting, and the lesions lead to restrictive chioloalveolar carcinoma, can present as a peripheral tumor
lung disease. that can mimic pneumonia. Most of these tumors are well
differentiated. Adenocarcinomas and large cell carcinomas
PBD9 721 BP9 505 PBD8 730–731 BP8 528 tend to be peripheral, but the former tend to produce a local-
ized mass, whereas cells of the latter are large and pleomor-
6 7 E The ALK gene encodes a receptor tyrosine kinase that phic and form sheets; sometimes it is difficult to distinguish
gets activated by fusion with the EML gene. The fused ALK- among them. Mesotheliomas almost always occur in the set-
EML (just as BCR-ABL in CML) can be targeted by inhibitors of ting of prior asbestos exposure; they are large pleural mass-
tyrosine kinases. Gain-of-function mutations in multiple genes es. Metastases tend to appear as multiple nodules. Squamous
encoding receptor tyrosine kinases, including EGFR, ALK, cell carcinomas occasionally can be peripheral (although
ROS, MET, and RET, are often mutated in adenocarcinomas, most are central) and are composed of pink, polygonal cells
which tend to be peripheral masses. Along with EGFR, ALK that have intercellular bridges. If well differentiated, squa-
gene mutations can be targeted in the subset of lung adeno- mous cell carcinomas show keratin pearls.
carcinomas that bear these molecular changes. All the other
genes, although more commonly mutated in a variety of can- PBD9 714–715 BP9 508 PBD8 725–727 BP8 531–534
cers, cannot be targeted by any of the available drugs.
7 1 D The patient probably has a small cell anaplastic (oat
PBD9 605, 714 BP9 506–509 PBD8 726–727 BP8 531 cell) carcinoma of the lung, which is most likely to produce
C H A P T E R 1 5 The Lung 2 5 1
a paraneoplastic syndrome with the syndrome of inappro- sarcoma can involve the lung in some patients with AIDS, and
priate secretion of antidiuretic hormone (SIADH), marked the tumor often has a bronchovascular distribution; obstruction
by free water retention with hyponatremia. Oat cell cancers is not common, but bleeding on biopsy is. Large-cell carcino-
tend to be central masses, and they are strongly associated mas are typically large, bulky, peripheral masses.
with smoking. Upper lobe cavitation suggests secondary
tuberculosis. Diaphragmatic pleural plaques can be a feature of PBD9 719–720 BP9 510–511 PBD8 729–730 BP8 534–535
pneumoconioses, particularly asbestosis. Infiltrates can suggest
an inflammatory process. Pneumothorax is most likely to occur 7 5 F The pleural fluid findings are typical of chylothorax,
from chest trauma, not from a neoplasm. A subpleural nodule which is uncommon but distinctive. Lymph fluid is rich in
with hilar adenopathy is the classic Ghon complex of primary lymphocytes, protein, and lipid (chylomicrons). Disruption
tuberculosis, which is unlikely to manifest with hemoptysis. of the thoracic duct in the posterior chest is most likely to
An air-fluid level suggests liquefaction in an abscess. cause chylothorax, and malignant neoplasms, such as a non-
Hodgkin lymphoma, are most likely to do this. An empyema
PBD9 713–715, 717, 719 BP9 509–510 PBD8 726–727 is composed of pus formed from neutrophilic exudation and
BP8 530–533 would appear cloudy and yellow. Congenital heart disease
can lead to congestive heart failure with a serous effusion.
7 2 C Horner syndrome is a result of sympathetic auto- Aortic dissection is an acute condition that can produce a
nomic nerve involvement by invasive pulmonary carcinoma. hemothorax. Cirrhosis is more likely to be associated with
Such a neoplasm in this location with these associated find- ascites or liver failure with hypoalbuminemia leading to hy-
ings is called a Pancoast tumor. Infectious processes such as drothorax. Miliary tuberculosis is seen as a reticulonodular
pneumonia are unlikely to impinge on structures outside the pattern on a chest radiograph; tuberculosis may produce
lung. Bronchiectasis destroys bronchi within the lung. Sar- hemorrhagic effusions.
coidosis can result in marked hilar adenopathy with a mass
effect, but involvement of the peripheral nervous system is PBD9 722 BP9 511–512 PBD8 732 BP8 535
unlikely. Likewise, tuberculosis is a granulomatous disease
that can lead to hilar adenopathy, although usually without 76 B The pleural fluid findings with low protein, low
destruction of extrapulmonary tissues. LDH, and low cell count are consistent with a transu-
date with hydrothorax. His hypertension has likely led to
PBD9 718–719 BP9 510 PBD8 728–729 BP8 532 left ventricular failure with pulmonary edema, and long-
standing left ventricular failure can lead to right ventricu-
73 B Hamartomas are uncommon but benign peripheral le- lar failure with body cavity effusions and peripheral edema.
sions of the lung. They are composed of benign-appearing epithe- Granulomatous diseases, including tuberculosis, along with
lial cells and connective tissue, typically with a large component carcinomas that are primary or metastatic to pleura, tend
of cartilage. They are included in the differential diagnosis of a to produce cellular effusions with numerous RBCs. Meso-
“coin lesion” that also includes carcinoma and granuloma. Ad- thelioma is likely to shed numerous cells into the pleural
enocarcinoma is the most common primary lung malignancy in cavity, although in most cases there is dense tumor that oblit-
nonsmokers, and it can manifest as a coin lesion, but it is com- erates the pleural cavity. Lymphomas may block lymphatics,
posed of gland-forming, malignant cells without cartilage. It tends including the thoracic duct, to produce a milky chylothorax
to be peripheral, making surgical resection an option in many with lipid and leukocytes. Bacterial pneumonias spreading
cases. Large cell carcinomas also are more likely to be peripheral, to the pleura are likely to produce an exudative effusion with
but they tend to be larger masses, with poorly differentiated cells. numerous leukocytes, predominantly neutrophilic.
Malignant mesothelioma is a rare neoplasm, even in individuals
who have been exposed to asbestos, and it arises on the pleura. PBD9 722 BP9 511 PBD8 535–536 BP8 534–535
Primary non-Hodgkin lymphomas of the lung are uncommon,
but may involve hilar or mediastinal lymph nodes. Some squa- 77 A Malignant mesothelioma is a rare tumor even in
mous cell carcinomas can be peripheral, but they are most likely individuals with a history of asbestos exposure. The tu-
to occur in individuals who smoke. mor may appear decades after exposure, and is not related
to amount or length of exposure. Bronchogenic carcinoma
PBD9 720 BP9 163 PBD8 730 BP8 528 is more common in individuals with asbestos exposure,
particularly when there is a history of smoking. Bird dust
7 4 B Most pulmonary carcinoids are central obstructing inhalation can lead to hypersensitivity pneumonitis. Coal
masses involving a large to medium-sized bronchus. These dust inhalation can lead to marked anthracosis, but without
neuroendocrine tumors have unpredictable behavior, but many a significant risk of lung cancer. Inhalation of cotton fibers
are localized, resectable, and follow a benign course. They typi- (byssinosis) leads to symptoms resembling asthma related to
cally manifest with hemoptysis and the consequences of bron- bronchoconstriction. Ozone and nitrogen oxides in smog can
chial obstruction. In this case, the pneumonia in the right upper cause acute respiratory discomfort, but are not known to be
lobe probably resulted from obstruction to drainage caused by promoters of neoplasia. Silicosis is typified by interstitial fi-
the tumor. Obstruction may lead to peripheral resorption at- brosis and causes a slight increase in the risk of bronchogenic
electasis. Adenocarcinomas are common lung tumors, but are carcinoma.
typically peripheral. A hamartoma is an uncommon but be-
nign pulmonary lesion that also is located peripherally. Kaposi PBD9 723–724 BP9 512 PBD8 733–734 BP8 536
2 5 2 U N I T I I Diseases of Organ Systems
7 8 F The solitary fibrous tumor, or localized mesothelio- hamartoma is a peripheral intraparenchymal mass with a sig-
ma, of pleura (or peritoneum) is a rare neoplasm that appears nificant component of fibrous connective tissue and usually
as a pedunculated mass. There is no relationship to asbestos with cartilage present. Hodgkin lymphoma is more likely to
exposure or other environmental pathogens. Many do not re- involve lymph nodes in the mediastinum. A malignant me-
cur or metastasize following resection, but larger tumor size, sothelioma forms a pleural mass that is not circumscribed;
higher mitotic count, and greater patient age (>55 years) in- the cells are atypical and cytokeratin positive. Metastases are
crease the risk for metastasis. Bronchioloalveolar carcinomas typically multiple and often produce bloody effusions.
are peripheral (but intraparenchymal) masses with atypical
epithelial cells growing along the framework of the lung. A PBD9 723 PBD8 732–733
16C H A P T E R
Head and Neck
PBD9 Chapter 16 and PBD8 Chapter 16: Head and Neck
BP9 Chapter 14 and BP8 Chapter 15: Oral Cavity and Gastrointestinal Tract
1 A 47-year-old man sees his dentist for a routine checkup. 4 A 23-year-old primigravida has noticed a rapidly en-
He states that his gums bleed easily on brushing his teeth. On larging nodule next to a tooth for the past 16 days. On physical
examination, he is found to have marked gingival recession examination there is a 1-cm, soft, reddish, pedunculated mass
with erythema, along with extensive plaque and calculus for- above a left upper bicuspid. She is advised that the lesion will
mation over tooth surfaces. Which of the following organisms likely regress. Which of the following pathologic findings is
is most likely to be associated with development of his oral most likely found in this lesion?
lesions? A Granulation tissue
A Actinobacillus B Lymphoid proliferation
B Candida C Neutrophilic exudate
C Epstein-Barr virus D Rhabdomyosarcoma
D Herpes simplex virus E Squamous hyperplasia
E Human papillomavirus 5 A 25-year-old man notices several 0.3-cm, clear vesicles
F Mucor circinelloides on his upper lip after a bout of influenza. The vesicles rupture,
leaving shallow, painful ulcers that heal over the course of 10
2 A 17-year-old girl notices a small, sensitive, gray-white days. Three months later, after a skiing trip, similar vesicles
area forming along the lateral border of her tongue 2 days be- develop, with the same pattern of healing. Which of the fol-
fore the end of her final examinations. On examination by the lowing microscopic findings is most likely to be associated
physician’s assistant, the girl is afebrile. There is a shallow, ul- with these lesions?
cerated, 0.3-cm lesion with an erythematous rim. No specific A Budding cells with pseudohyphae
therapy is given, and the lesion disappears within 2 weeks. B Mononuclear inflammatory infiltrates
The history shows that the girl does not use tobacco or alcohol. C Neutrophils within abscesses
Which of the following is the most probable diagnosis? D Squamous epithelial hyperkeratosis
A Aphthous ulcer E Intranuclear inclusions
B Herpes simplex stomatitis 6 A 35-year-old, HIV-positive man complains that he has
C Leukoplakia had a “bad” taste in his mouth and discoloration of his tongue
D Oral thrush for the past 6 weeks. On physical examination, there are areas
E Sialadenitis of adherent, yellow-to-gray, circumscribed plaque on the lat-
eral aspects of the tongue. This plaque can be scraped off as a
3 A 55-year-old woman notes a nodule while rubbing her pseudomembrane to show an underlying granular, erythema-
tongue on the side of her mouth. On physical examination by tous base. What is the most likely diagnosis?
her dentist, there is a firm, nontender 0.6-cm nodule covered A Aphthous ulcer
by pink buccal mucosa at the bite line next to the first molar on B Cheilosis
the lower right. The lesion is excised and does not recur. What C Hairy leukoplakia
is the most likely diagnosis? D Herpetic stomatitis
A Candidiasis E Leukoplakia
B Fibroma F Oral thrush
C Leukoplakia
D Pyogenic granuloma 253
E Sialadenitis
2 5 4 U N I T I I Diseases of Organ Systems 9 A 51-year-old man from Kolkata has an area of depres-
sion in his mouth that has enlarged over the past 7 months.
7 A 42-year-old man has had a constant bad taste in his On oral examination, there is a 1.5 × 0.7 cm velvety, erythema-
mouth for the past month. On physical examination there are tous area with focal surface erosion on his left buccal mucosa.
white fluffy patches on the sides of his tongue. These cannot The lesion is excised and on microscopic examination there is
be scraped off. A biopsy is taken and on microscopic examina- dysplastic squamous epithelium. Which of the following is the
tion shows squamous epithelial hyperkeratosis, parakeratosis, most likely risk factor for developing this lesion?
and koilocytosis. Immunohistochemical staining for Epstein- A Candidiasis
Barr virus (EBV) is positive. Which of the following is the most B Dental malocclusion
likely risk factor for his oral lesions? C Epstein-Barr virus infection
A Chronic alcohol abuse D Immunosuppression
B Diabetes mellitus E Eating hot, spicy food
C HIV infection F Tobacco chewing
D Pernicious anemia
E Sjögren syndrome
A
B 10 A 49-year-old man has used chewing tobacco and snuff
for many years. On physical examination the lesion shown in
8 A 58-year-old man, a cigar smoker, visited his dentist for the figure is seen on the hard palate. It cannot be removed by
a routine dental examination. The dentist noticed lesions with scraping. A biopsy is performed, and microscopic examination
the clinical (A) and histologic (B) appearance shown in the fig- of the lesion shows a thickened squamous mucosa. Four years
ure. The medical history showed no major medical problems. later, a biopsy specimen of a similar lesion shows carcinoma in
Which of the following etiologic factors most likely contrib- situ. Which of the following is the most likely diagnosis?
uted to the development of these lesions? A Oral thrush
A Chronic sialadenitis B Lichen planus
B Dental caries C Leukoplakia
C Eating smoked foods D Pyogenic granuloma
D Herpes simplex virus type 1 E Xerostomia
E Smoking tobacco
11 A 54-year-old man, a nonsmoker, has a nonheal-
ing ulceration at the base of his tongue on the right side for
2 months. On examination this lesion is 1 cm in diameter
with irregular borders. Biopsy of the lesion is performed and
microscopic examination shows infiltrating squamous cell car-
cinoma. Which of the following infectious agents is most likely
to be associated with this lesion?
A Candida albicans
B Herpes simplex virus (HSV)
C Human papillomavirus (HPV)
D Prevotella intermedia
E Group A streptococcus
12 A 19-year-old woman has noted swelling in the back of C H A P T E R 1 6 Head and Neck 2 5 5
her mouth for 2 months. On dental examination, she has an
area of swelling in the location of the left third molar. Dental 16 On December 13, 1799, George Washington, recently
radiographs show a radiolucent unilocular, well-circumscribed retired as first President of the United States, developed a
cyst surrounding the crown of the unerupted third mandibular “cold” with mild hoarseness. By the next morning he had dif-
molar. The lesion is excised, and on microscopic examination, ficulty breathing and swallowing, with throat pain. He was
the cyst is lined by stratified squamous epithelium and sur- treated with the usual therapy of the time: bloodletting. Had
rounded by a chronic inflammatory infiltrate. What is the most vital signs been recorded, they may have shown temperature
likely diagnosis? of 37.8° C, pulse 115/min, respiratory rate 24/min, and blood
A Ameloblastoma pressure 90/60 mm Hg. Which of the following organisms
B Dentigerous cyst most likely caused his illness?
C Odontogenic keratocyst A Coronavirus
D Odontoma B Corynebacterium diphtheriae
E Periapical cyst/granuloma C Haemophilus influenzae
D Parainfluenza virus
13 A 19-year-old man noted progressive swelling on the E Prevotella intermedia
left side of his face over the past year. On physical examina- F Group A streptococcus
tion, there is painless swelling in the region of the left posterior
mandible. Head CT scan shows a circumscribed multilocular 17 A 3-year-old child has had difficulty breathing for the
cyst of the left mandibular ramus. The lesion is surgically past 24 hours. On physical examination, the child is febrile
e xcised with wide bone margins. On microscopic examination, and has a harsh cough with prominent inspiratory stridor.
the lesion shows cysts lined by stratified squamous epithelium The lungs are clear on auscultation. An anterior-posterior
with a prominent basal layer; no inflammation or granulation neck radiograph shows the steeple sign caused by edema pro-
tissue is seen. What is the most likely diagnosis? ducing loss of normal shoulders on the subglottic larynx. The
A Ameloblastoma child’s oxygen saturation is normal with pulse oximetry. She
B Dentigerous cyst improves over the next 3 days while taking nebulized gluco-
C Odontogenic keratocyst corticoids. Which of the following organisms is the most likely
D Odontoma cause of the child’s condition?
E Periapical cyst/granuloma A Corynebacterium diphtheriae
B Epstein-Barr virus
14 A 26-year-old man has had difficulty breathing through C Haemophilus influenzae
his nose for 3 years, but this problem has become progressive- D Human papillomavirus
ly worse over the past 2 months. Physical examination shows E Parainfluenza virus
glistening, translucent, polypoid masses filling the nasal F Streptococcus, group A
cavities. Histologic examination of the excised masses shows
r espiratory mucosa overlying an edematous stroma with scat- 18 A 9-year-old girl has had a sore throat for the past
tered plasma cells and eosinophils. Which of the following 2 days. On physical examination there is pharyngeal erythema
laboratory findings is most likely to be present in this patient? with yellowish exudates over swollen palatine tonsils. A Gram
A Elevated serum hemoglobin A1c level stain of the exudate shows gram-positive cocci in chains. She is
B Increased serum IgE level given penicillin therapy. What is the most likely complication
C Nuclear staining for Epstein-Barr virus antigens prevented by prompt treatment of this girl?
D Positive ANA test result A Carditis
E Tissue culture positive for Staphylococcus aureus B Hepatitis
C Meningitis
15 A 39-year-old woman has been bothered by headache, D Otitis
facial pressure, nasal obstruction with discharge, and di- E Pneumonitis
minished taste sensation for the past 6 months. On physical
examination there is discomfort on palpation over her left
maxillary sinus. No oral lesions are noted. Rhinoscopy shows
nasal erythema, marked edema, and purulent discharge.
Which of the following complications is most likely to occur in
this patient?
A Mucocele
B Nasopharyngeal carcinoma
C Osteomyelitis
D Sinonasal papilloma
E T-cell lymphoma
2 5 6 U N I T I I Diseases of Organ Systems 22 A 58-year-old man bothered by increasing hoarseness
for almost 6 months now has an episode of hemoptysis. On
19 A 48-year-old man from Hong Kong has had difficulty physical examination, no lesions are noted in the nasal or
breathing through his nose and has experienced dull facial oral cavity. There is a firm, nontender anterior cervical lymph
pain for the past 4 months. On physical examination, there is a node. The lesion shown in the figure is identified by endosco-
mass filling the right nasal cavity. CT scan of the head shows py. The patient undergoes biopsy, followed by laryngectomy
a 5-cm mass in the nasopharynx on the right that erodes adja- and neck dissection. Which of the following etiologic factors
cent bone. The mass is excised, and microscopic examination most likely played the greatest role in the development of this
shows that it is composed of large epithelial cells with indis- lesion?
tinct borders and prominent nuclei. Mature lymphocytes are A Epstein-Barr virus infection
scattered throughout the undifferentiated neoplasm. Which of B Human papillomavirus infection
the following etiologic factors most likely played the greatest C Repeated bouts of aspiration
role in the development of this lesion? D Smoking tobacco
A Allergic rhinitis E Type I hypersensitivity
B ANCA-associated vasculitis
C Epstein-Barr virus infection 23 A 5-year-old boy has had repeated bouts of earache
D Sjögren syndrome for 3 years. Each time on examination, the bouts have been
E Smoking tobacco accompanied by a red, bulging tympanic membrane, either
unilaterally or bilaterally, sometimes with a small amount of
20 A 28-year-old man who is a singer/songwriter has been yellowish exudate. Laboratory studies have included cultures
experiencing hard times for the past 3 years. He has played at of Staphylococcus aureus, Pseudomonas aeruginosa, and Moraxella
a couple of clubs a night to earn enough to avoid homeless- catarrhalis. The most recent examination shows that the right
ness. He comes to the free clinic because he has noticed that tympanic membrane has perforated. The boy responds to an-
his voice quality has become progressively hoarser over the tibiotic therapy. Which of the following complications is most
past year. On physical examination, he is afebrile. There are no likely to occur as a consequence of these events?
palpable masses in the head and neck area. He does not have A Cholesteatoma
a cough or significant sputum production, but he has been ad- B Eosinophilic granuloma
vised on previous visits to give up smoking. Which of the fol- C Labyrinthitis
lowing is most likely to produce these findings? D Otosclerosis
A Croup E Squamous cell carcinoma
B Epiglottitis
C Reactive nodule
D Squamous cell carcinoma
E Squamous papillomatosis
21 A 6-year-old boy has had increased difficulty breath-
ing, and the character of his voice has changed over the past
3 months. Endoscopic examination shows three soft, pink ex-
crescences on the true vocal cords and in the subglottic region.
The masses are 0.6 to 1 cm in diameter. Microscopic exami-
nation of the excised masses shows fingerlike projections of
orderly squamous epithelium overlying fibrovascular cores.
Immunostaining for human papillomavirus 6 antigens is posi-
tive. Based on these findings, which of the following state-
ments is the best advice to give the parents of this boy?
A A total laryngectomy is necessary
B Congenital heart disease may be present
C The boy should not overuse his voice
D The lesions are likely to recur
E Therapy with acyclovir is indicated
24 A 64-year-old man has had progressive difficulty hear- C H A P T E R 1 6 Head and Neck 2 5 7
ing, particularly with the left ear, over the past 10 years. Au-
diometric testing shows that he has a bone conduction type of 28 A 67-year-old man with Parkinson disease has experi-
deafness. CT scan of the head shows no abnormal findings. enced an increasingly dry mouth for the past 3 months, and
The patient’s brother and mother are similarly affected. What this interferes with eating and swallowing. He has noted dry
is the most likely diagnosis? eyes as well. On physical examination he has minimal tremor
A Cholesteatoma at rest; there are no other abnormal findings. Laboratory stud-
B Chondrosarcoma ies show no detectable autoantibodies. Which of the following
C Otitis media is the most likely cause for his findings?
D Otosclerosis A Alcohol ingestion
E Schwannoma B Anticholinergic drug use
C Candidiasis
25 A 25-year-old woman is concerned about a lump on the D Sialadenitis with blockage of salivary duct
left side of her neck that has remained the same size for the E Sjögren syndrome
past year. Physical examination shows a painless, movable, F Tobacco use
3-cm nodule beneath the skin of the left lateral neck just above
the level of the thyroid cartilage. There are no other remark- 29 A 69-year-old man has a major psychosis. He has been
able findings. Fine-needle aspiration of the mass is performed. bothered by pain on the left side of the face for 2 weeks. On
Her physician is less than impressed by the pathology report, physical examination, there is a tender area of swelling 4 cm
which notes, “Granular and keratinaceous cellular debris.” in diameter beneath the skin, anterior to the left auricle above
Fortunately, she has saved her Robbins pathology textbook the angle of the jaw. CT scan of the head shows cystic and
from medical school. She consults the head and neck chapter solid areas in the region of an enlarged left parotid gland.
to arrive at a diagnosis, using the data from the report. Which After a course of antibiotic therapy, there is only minimal
of the following terms best describes this nodule? improvement. A parotidectomy is performed. Microscopic
A Branchial cyst examination of the excised gland shows acute and chronic
B Metastatic thyroid carcinoma inflammation, with fibrosis and abscess formation, duct lithi-
C Mucocele asis, and atrophy of acini. Which of the following infectious
D Mucoepidermoid tumor agents is most likely to be found in this gland?
E Paraganglioma A Epstein-Barr virus
F Thyroglossal duct cyst B Human papillomavirus
C Prevotella intermedia
26 A 17-year-old girl is concerned about a “bump” on her D Rubeola virus
neck that she has noticed for several months. It does not seem E Staphylococcus aureus
to have increased in size during that time. On physical ex-
amination, there is a discrete, slightly movable nodule in the 30 A 95-year-old man has noted swelling of his lower lip
midline of the neck just adjacent to the region of the hyoid. for the past month. On examination, there is a fluctuant, 1-cm
The nodule is excised, and microscopic examination shows nodule with a blue, translucent hue just beneath the oral mu-
a cystic mass lined by squamous and respiratory epithelium cosa on the inside of his lip. The lesion is excised, and on mi-
surrounded by fibrous tissue with lymphoid nodules. Which croscopic examination shows granulation tissue. What is the
of the following additional histologic elements would most most likely etiology for this lesion?
likely be located adjacent to this cyst? A Eating chili peppers
A Malignant lymphoma B French kissing
B Noncaseating granulomas C HIV infection
C Serous salivary glands D Local trauma
D Squamous cell carcinoma E Pipe smoking
E Thyroid follicles
31 A 65-year-old woman has noticed a slowly enlarging
27 A 56-year-old woman has noticed an enlarging lump on the nodule on her face for the past 3 years. On physical examina-
right side of her neck for the past 7 months. On physical examina- tion, a 3-cm, nontender, mobile, discrete mass is palpable on
tion, there is a 3-cm nodule in the right upper neck, medial to the the left side of the face, anterior to the ear and just superior to
sternocleidomastoid muscle and lateral to the trachea at the angle the mandible. The mass is completely excised, and histologic
of the mandible. CT scan shows a circumscribed, solid mass ad- examination shows ductal epithelial cells in a myxoid stroma
jacent to the carotid bifurcation. Microscopic examination of the containing islands of chondroidlike tissue and bone. This pa-
excised mass shows nests of round cells with pink, granular cy- tient is most likely to have which of the following neoplasms?
toplasm. Tests for immunohistochemical markers chromogranin A Acinic cell tumor
and S-100 are positive. Electron microscopy shows neurosecretory B Mucoepidermoid carcinoma
granules in the tumor cell cytoplasm. The tumor recurs 1 year lat- C Pleomorphic adenoma
er and is again excised. What is the most likely diagnosis? D Primitive neuroectodermal tumor
A Metastatic squamous cell carcinoma E Squamous cell carcinoma
B Metastatic thyroid medullary carcinoma F Warthin tumor
C Mucoepidermoid carcinoma
D Paraganglioma
E Warthin tumor
2 5 8 U N I T I I Diseases of Organ Systems
33 A 60-year-old woman noticed an enlarging “bump” be-
neath her tongue for the past year. She does not smoke or use
alcohol. On physical examination, there is a 2.5-cm, movable,
submucosal mass arising in the minor salivary glands on the
buccal mucosa beneath the tongue on the right. Histologic ex-
amination of the excised mass shows that it is malignant and
locally invasive. The tumor recurs within 1 year. Which of the
following is the most likely diagnosis?
A Non-Hodgkin lymphoma
B Mucoepidermoid carcinoma
C Primitive neuroectodermal tumor
D Pleomorphic adenoma
E Squamous cell carcinoma
F Warthin tumor
32 A 57-year-old man notices a lump on the right side of
his face that has become larger over the past year. On physical
examination, a 3- to 4-cm firm, mobile, painless mass is pal-
pable in the region of the right parotid gland. The oral mucosa
appears normal. He does not complain of difficulty in chewing
food or talking. The mass is completely excised, and histologic
examination shows the findings in the figure. What is the most
likely diagnosis?
A Mucoepidermoid carcinoma
B Non-Hodgkin lymphoma
C Pleomorphic adenoma
D Sialolithiasis
E Sjögren syndrome
F Warthin tumor
ANSWERS history is a cautionary note for all young people. Oral thrush
is a superficial candidal infection that occurs in diabetic, neu-
1 A Periodontitis becomes more prevalent with age, often tropenic, and immunocompromised patients. Inflammation of
secondary to the effects of dental plaque formation driven by a salivary gland (sialadenitis), typically a minor salivary gland
oral flora. The gingival recession increases the risk for dental in the oral cavity, may produce a localized, tender nodule.
caries. Regular dental cleanings to remove the plaque and
regular gentle tooth brushing help to slow the progression PBD9 728 BP9 552 PBD8 742 BP8 580
of periodontitis. Some periodontitis cases arise in the setting
of systemic disease. Candidiasis is seen in immunocompro- 3 B Chronic irritation is the most likely cause for an “ir-
mised individuals and often forms an inflammatory mem- ritation” fibroma of the buccal mucosa, which is due to con-
brane on the tongue. Epstein-Barr virus has been associated nective tissue hyperplasia. Oral thrush from candidiasis
with development of hairy leukoplakia. Herpes simplex vi- produces white-to-gray plaques on the tongue. Leukoplakia
rus results in vesicles that can rupture and form superficial is hyperplasia of the squamous epithelium and appears as
ulcers on oral mucosa. Human papillomavirus can drive a white plaque or patch, and can be premalignant. A pyo-
squamous epithelial hyperplasia, dysplasia, and carcinoma. genic granuloma is a reddish nodule of granulation tissue
Mucor has broad, nonseptated hyphae and can result in si- on the gingiva, and it often ulcerates. A minor salivary gland
nusitis, particularly in the setting of ketoacidosis. could become obstructed, producing a mucocele, or become
inflamed and tender (sialadenitis).
PBD9 728 PBD8 741
PBD9 728–729 BP9 552–553 PBD8 741–742
2 A An aphthous ulcer is a common lesion that also is
known as a canker sore. The lesions are never large, but are an- 4 A A pyogenic granuloma may begin to enlarge abruptly
noying and tend to occur during periods of stress. Aphthous and increase in size rapidly, which can be alarming, but the
ulcers are not infectious; they probably have an autoimmune process is benign and often regresses, or resolves into fibrous
origin. Herpetic lesions are typically vesicles that can rupture. connective tissue. Though there are both acute and chronic
Leukoplakia appears as white patches of thicker mucosa from inflammatory cells within this granulation tissue, neither
hyperkeratosis. It may be a precursor to squamous cell carci-
noma in a few cases. The temperance ditty mentioned in the
C H A P T E R 1 6 Head and Neck 2 5 9
predominates. Rhabdomyosarcoma is more likely to be a smoking. Infections and inflammation are not recognized
childhood tumor, and sarcomas in adults are more likely to oc- risk factors for oral leukoplakia or oral squamous cell can-
cur in deep soft tissues. This reddish nodule is not leukoplakia, cers. Dental caries is not a risk factor for leukoplakia, unless
which is a white plaque from squamous epithelial hyperplasia. the affected tooth becomes eroded and misshapen. The type
of food eaten has less of a correlation with cancer of the oral
PBD9 729–730 BP9 553 PBD8 741–742 cavity than with cancer of the esophagus.
5 E The lesions of herpes simplex virus type 1 (HSV-1), PBD9 731 BP9 553–554 PBD8 744–745 BP8 581–582
also known as cold sores or fever blisters, are common. Many
individuals have been infected with HSV-1, which is latent, 9 F Erythroplakia is a premalignant lesion that is more
and the oral and perianal lesions appear during periods of likely to progress to squamous carcinoma than leukoplakia,
stress. Recurrence of herpes labialis is the norm. Budding but the major risk factors are the same: tobacco, alcohol, in-
cells with pseudohyphae suggest a candidal infection with sufficient fruit intake, and betel nut. Countries of the Indian
oral thrush. A mononuclear infiltrate is nonspecific and can subcontinent have the highest incidence, accounting for up
be seen with aphthous ulcers. Atypical lymphocytes are seen to 10% of all cancers in those populations. Of the remaining
with infectious mononucleosis. They may be accompanied options, dental malocclusion may lead to leukoplakia. The
by a rash, but do not produce vesicular lesions of the skin. oral infections listed are not premalignant, but may be found
Neutrophilic abscesses suggest bacterial infection. Leukopla- with immunosuppression. Dietary fruit tends to mitigate the
kia is marked by hyperkeratosis. risk, but spices have no effect either way.
PBD9 729 BP9 552 PBD8 742–743 BP8 580–581 PBD9 731 BP9 553–554 PBD8 744–745 BP8 581–582
6 F Oral thrush is a common but not life-threatening 10 C The raised white patches suggest leukoplakia. This is
condition, resulting from oral candidiasis in immunocom- a premalignant condition. Risk factors include tobacco use,
promised individuals. The lesion is typically superficial. particularly tobacco chewing, and chronic irritation. Human
M icroscopic examination shows the typical budding cells papillomavirus infection has been implicated in some l esions.
and pseudohyphae of Candida. Aphthous ulcers, or canker Oral thrush appears most often on the tongue of immuno-
sores, are very common in young individuals, but can a ppear compromised individuals as a yellowish plaquelike area.
at any age; they tend to be recurrent superficial ulcerations. M icroscopic examination shows budding cells with pseudo-
Cheilosis is fissuring or cracking of the mucosa, typically hyphae characteristic of Candida infection. Lichen planus in
at the corners of the mouth, which may be seen with vita- the oral cavity usually appears with similar skin lesions; it
min B2 (riboflavin) deficiency. Hairy leukoplakia also can forms whitish patches that may ulcerate. The lesions have
be seen with HIV infection, but it is far less common than intense submucosal chronic inflammation. A pyogenic gran-
oral thrush. It occurs from marked hyperkeratosis, forming a uloma forms a painful gingival nodule of granulation tissue.
rough “hairy” surface, and is related to Epstein-Barr virus in- Xerostomia, or “dry mouth,” is seen in Sjögren syndrome.
fection. Multinucleated cells suggest a herpesvirus infection,
which typically has vesicles that ulcerate. A typical squamous PBD9 731 BP9 553–554 PBD8 744–745 BP8 581–582
epithelial cells usually arise from areas of oral leukoplakia.
11 C Smoking and alcoholism are frequent etiologies for
PBD9 729–730 BP9 552 PBD8 743 BP8 581 oral squamous cell carcinomas, and mutations in the TP53
gene are often present. However, in nonsmokers, HPV infec-
7 C Oral hairy leukoplakia is seen in immunocompro- tion may be implicated, along with overexpression of p16.
mised persons. It presages AIDS in persons who are HIV- The good news: the oral carcinomas arising with HPV have
positive. Chronic alcohol and/or tobacco use are associated a better prognosis, though they may be multifocal and recur.
with oral squamous cell carcinomas. Type 1 diabetes mel- The better news: vaccination against HPV may help prevent
litus with ketoacidosis is associated with fungal sinusitis, this disease. Oral candidiasis (thrush) may occur in immu-
particularly with mucormycosis. Pernicious anemia from vi- nocompromised persons. HSV causes self-limited acute
tamin B12 deficiency is associated with glossitis that is mainly gingivostomatitis (cold sores). The genus Prevotella includes
atrophic. Sjögren syndrome leads to inflammation and atro- anaerobes that are associated with periodontitis and with
phy of salivary glands leading to xerostomia with atrophy, buccal infections that become cellulitis (Ludwig angina).
fissuring, and ulcerations in the oral cavity mucosa. Strep throat is an acute exudative pharyngitis that has the
immunologic complications of rheumatic heart disease or
PBD9 730 BP9 554 PBD8 743 BP8 581 postinfectious glomerulonephritis.
8 E This whitish, well-defined mucosal patch on the tongue PBD9 731–733 BP9 554 PBD8 746 BP8 582–583
has the characteristic appearance of leukoplakia, a premalig-
nant lesion that can give rise to squamous cell carcinoma. Use 12 B A dentigerous cyst typically occurs in young persons
of tobacco products is implicated in the development of leu- when teeth are erupting, particularly molars. It is benign and
koplakia. Chronic alcohol abuse also is implicated, but the does not recur following complete excision. Dentigerous cysts
association is less strong than with tobacco. Ill-fitting den- originate around the crown of an unerupted tooth, typically
tures may lead to leukoplakia, but far less commonly than the third molar, and are lined by a thin, nonkeratinizing layer
2 6 0 U N I T I I Diseases of Organ Systems
of squamous epithelium; they contain a dense chronic inflam- care has advanced since the year 1799, but it has been little more
matory infiltrate in the stroma. An odontogenic keratocyst that than a hundred years that medical care has done more good
arises from rests of odontogenic epithelium within the jaw and than harm. Haemophilus influenzae may cause inflammation
is benign, but can recur if inadequately excised. Ameloblas- with an abrupt onset of pain and possible airway obstruction,
toma and odontoma are tumors arising from odontogenic epi- particularly in children. In adults, the airway is typically large
thelium. Odontoma, the most common odontogenic tumor, enough to preclude marked obstruction. Thus, Washington’s
shows extensive deposition of enamel and dentin. Periapical illness was survivable, but the treatments he received at that
cysts/granulomas are inflammatory lesions that develop at time in history (bloodletting, purgatives, blistering agents) con-
the apex of teeth as complications of long-standing pulpitis. tributed to his demise. This cautionary tale supports the adage:
if you don’t know what you’re doing, then stop. Coronaviruses
PBD9 734 BP9 557–558 PBD8 748 are best known to cause the common cold. Corynebacterium diph-
theriae is the cause of diphtheria, which produces laryngitis with
1 3 C An odontogenic keratocyst arises from rests of odon- a characteristic dirty gray membrane that may slough and be as-
togenic epithelium within the jaw. It is benign, but can recur pirated. This infection is now rare because of routine childhood
if inadequately excised. Ameloblastoma and odontoma are immunizations. Another cause for epiglottitis is parainfluenza
tumors arising from odontogenic epithelium. Odontoma, virus, which has no vaccine, and is best known as the cause for
the most common odontogenic tumor, shows extensive de- croup in children. The genus Prevotella includes anaerobes that
position of enamel and dentin. Dentigerous cysts originate are associated with periodontitis and with buccal infections that
around the crown of an unerupted tooth, typically the third become cellulitis (Ludwig angina). Group A streptococci pro-
molar, and are lined by a thin, nonkeratinizing layer of squa- duce a strep throat that is an acute exudative pharyngitis.
mous epithelium; they contain a dense chronic inflammatory
infiltrate in the stroma. Periapical cysts/granulomas are in- PBD9 736 BP9 512–513 PBD8 743 BP8 537
flammatory lesions that develop at the apex of teeth as com-
plications of long-standing pulpitis. 17 E The child has croup, a laryngotracheobronchitis that
is most often caused by parainfluenza virus. The inflamma-
PBD9 734 BP9 557 PBD8 748–749 tion may be severe enough to produce airway obstruction.
Corynebacterium diphtheriae is the cause of diphtheria, which
14 B Inflammatory nasal polyps can be associated with re- produces laryngitis with a characteristic dirty gray mem-
current allergic rhinitis, a form of type I hypersensitivity often brane that may slough and be aspirated. This infection is now
called hay fever. Type I hypersensitivity is associated with high rare because of routine childhood immunizations. Epstein-
IgE levels in the serum. The elevated hemoglobin A1c level in- Barr virus may be associated with infectious mononucleosis
dicates diabetes mellitus. Diabetes is not a risk factor for polyp and produce pharyngitis. Epstein-Barr virus also is associ-
formation, but ketoacidosis can lead to nasopharyngeal mucor- ated with nasopharyngeal carcinoma. Haemophilus influenzae
mycosis. Epstein-Barr virus infection can be found in nasopha- may cause an acute bacterial epiglottitis with an abrupt onset
ryngeal carcinomas. Autoimmune diseases are not associated of pain and possible airway obstruction. Human papilloma-
with nasal polyp formation. Staphylococcus aureus often colo- virus is associated with laryngeal papillomatosis. Group A
nizes the nasal cavity, but it usually does not cause problems. streptococci produce an exudative pharyngitis.
PBD9 735–736 PBD8 749 PBD9 739 BP9 512–513 PBD8 752 BP8 537
15 C Chronic sinusitis is a common condition and may be 18 A She has a group A β-hemolytic streptococcal phar-
punctuated by episodes of acute sinusitis. Lack of smell with yngitis, and the feared complication is an autoimmune re-
nasal cavity inflammation often affects sensation of taste. sponse from molecular mimicry to streptococcal M proteins.
Once the cycle of inflammation, obstruction, stasis, mucocili- Rheumatic fever results 2 to 3 weeks later from formation
ary damage, and polymicrobial infection is established it be- of antibodies directed at endocardium, epicardium, and/
comes difficult to stop. Increased pressure with inflammation or myocardium (rheumatic heart disease). Poststreptococcal
in the sinus can erode into adjacent bone, causing osteomy- glomerulonephritis may also occur. The pharyngitis is un-
elitis. A mucocele filled with nonpurulent secretions is more likely to spread elsewhere or produce septicemia. Streptococ-
likely to occur in frontal and ethmoid sinuses. Sinusitis is not cus pneumoniae is more likely to produce meningitis, otitis,
a risk factor for malignancy. Nasopharyngeal carcinomas are and pneumonitis. Streptococci are unlikely to involve liver.
related to Epstein-Barr virus (EBV) infection. T-cell lympho-
mas typically occur in men and are EBV positive. Papillomas PBD9 736, 738 BP9 512–513 PBD8 750, 752 BP8 536–537
most often occur in men and have an exophytic growth pat-
tern, but those that are endophytic aggressively extend into 19 C Nasopharyngeal carcinoma has a strong association
adjacent soft tissue and bone, making removal difficult. with Epstein-Barr virus infection, which contributes to the
transformation of squamous epithelial cells. Allergic rhini-
PBD9 735–736 PBD8 750 tis is associated with development of nasal polyps, but these
do not become malignant. ANCA-associated vasculitis can
16 C George Washington likely succumbed to an acute bac- involve the respiratory tract, causing granulomatous inflam-
terial epiglottitis, which is now treatable but still life-threatening, mation and necrotizing vasculitis, but there is no risk of ma-
particularly in children, in whom it is more common. Medical lignant transformation. Sjögren syndrome is associated with
C H A P T E R 1 6 Head and Neck 2 6 1
malignant lymphomas, but these typically arise in the sali- ized by the presence of Langerhans cells. Labyrinthitis typi-
vary gland, not the nasal cavity. Smoking is not associated cally is caused by a viral infection and is self-limited. Oto-
with nasopharyngeal carcinoma, although it does contribute sclerosis is abnormal bone deposition in the ossicles of the
to oral and esophageal cancers. middle ear that results in bone deafness in adults.
PBD9 737–738 BP9 513 PBD8 751–752 BP8 537 PBD9 740 PBD8 754
20 C Reactive nodules (vocal cord polyps, or singer’s nod- 2 4 D Otosclerosis can be familial, particularly when it is
ules) occur most often in men who are heavy smokers or who severe. It results from fibrous ankylosis followed by bony
strain their vocal cords. The nodules are generally only a few overgrowth of the little ossicles (malleus, incus, stapes) of
millimeters in size and have a fibrovascular core covered by hy- the middle ear. A cholesteatoma is typically a unilateral pro-
perplastic and hyperkeratotic squamous epithelium. They are cess that complicates chronic otitis media in a child or young
not premalignant. Croup is an acute laryngotracheobronchitis adult. Uncomplicated otitis media is usually self-limited and
that most often occurs in children and produces airway nar- is uncommon in adults. Chondrosarcomas may involve the
rowing with inspiratory stridor. Epiglottitis is an acute inflam- skull in older adults, but are rare, solitary, bulky masses in the
matory process that may cause airway obstruction. Squamous region of the jaw. A schwannoma typically involves the ves-
cell carcinomas of the pharynx and larynx form irregular, ul- tibulocochlear nerve and results in a nerve conduction form of
cerating masses, are more common in smokers, but generally deafness. Schwannomas are usually unilateral, although famil-
are seen in individuals older than this patient. Squamous pap- ial neurofibromatosis could result in multiple schwannomas.
illomatosis usually first appears in childhood; if it is extensive,
it can produce airway obstruction. PBD9 740–741 PBD8 754
PBD9 739 BP9 513 PBD8 752 BP8 537 2 5 A Branchial cysts, also known as lymphoepithelial cysts,
may be remnants of an embryonic branchial arch or a sali-
2 1 D Recurrent respiratory papillomatosis is caused by hu- vary gland inclusion in a cervical lymph node. They are
man papillomavirus types 6 and 11. These lesions frequently distinguished from thyroglossal duct cysts by their lateral
recur after excision. They may regress after puberty. Laryn- location, the absence of thyroid tissue, and their abundant
geal papillomas arising in adulthood are usually solitary and lymphoid tissue. Occult thyroid carcinoma, often a papil-
do not recur. There is no effective antiviral therapy for human lary carcinoma, may manifest as a metastasis to a node in
papillomavirus. Although the lesions can arise throughout the neck, but the microscopic pattern is that of a carcinoma.
the airways, they are benign and do not become malignant. About 5% of squamous cell carcinomas of the head and neck
The occurrence of the lesions is not related to the use of the initially manifest as a nodal metastasis, without an obvious
voice, as is a laryngeal nodule, which is quite small. This is primary site. This patient is quite young for such an event,
not a congenital condition and is not part of a syndrome. however. Mucoceles form in minor salivary glands; muco-
epidermoid tumors form in salivary glands. The nodule in
PBD9 739 BP9 513–414 PBD8 752 BP8 537–538 this patient is in the neck. Paragangliomas are solid tumors
that may arise deep in the region of the carotid body near the
2 2 D The figure shows a large, fungating neoplasm that common carotid bifurcation.
has the typical appearance of a laryngeal squamous cell car-
cinoma. The most common risk factor is smoking, although PBD9 741 PBD8 755
chronic alcohol abuse also plays a role; some patients har-
bor human papillomavirus sequences. Invasive cancers arise 2 6 E A thyroglossal duct (tract) cyst is a developmen-
from squamous epithelial dysplasias. Epstein-Barr virus in- tal abnormality that arises from elements of the embryonic
fection is associated with nasopharyngeal carcinomas. Aspi- thyroglossal duct extending from the foramen cecum of the
ration may result in acute inflammation, but not neoplasia. tongue down to the thyroid gland. One or more remnants
Allergies with type I hypersensitivity may result in transient of this tract may enlarge to produce a cystic mass. Although
laryngeal edema, but not neoplasia. lymphoid tissue often surrounds these cysts, malignant
transformation does not occur. Granulomatous disease is
PBD9 739–740 BP9 514 PBD8 753 BP8 538 more likely to involve lymph nodes in the typical locations
in the lateral neck regions. Salivary gland choristomas are
2 3 A Cholesteatomas are not true neoplasms, but they unlikely at this site. The cysts may contain squamous epithe-
are cystic masses lined by squamous epithelium. The des- lium, but squamous cell carcinoma does not arise from such
quamated epithelium and keratin degenerates, resulting in a cyst. If there is a cystic lesion with lymphoid tissue and
cholesterol formation and giant cell reaction. Although their squamous carcinoma in the neck, it is probably a metastasis
histologic findings are benign, cholesteatomas can gradu- from an occult primary tumor of the head and neck.
ally enlarge, eroding and destroying the middle ear and sur-
rounding structures. They occur as a complication of chronic PBD9 741 PBD8 755
otitis media. Although cholesteatomas have a squamous epi-
thelial lining, malignant transformation does not occur. An 2 7 D Paragangliomas are neuroendocrine tumors that
eosinophilic granuloma of bone occasionally may be seen in rarely produce sufficient catecholamines to affect blood
the region of the skull in young children, but it is character- pressure, in contrast to their adrenal medullary counterpart,
2 6 2 U N I T I I Diseases of Organ Systems
pheochromocytoma. The microscopic appearance of these le- misaligned teeth or dentures also may produce leukoplakia.
sions does not always correlate with their biological behav- In some parts of the world, the chewing of betel nut is a risk
ior. There is a tendency for recurrence and metastasis despite factor for oral cancer.
the tumor’s “bland” appearance. Metastases always should
be considered in patients this age. About 5% of squamous PBD9 743 BP9 555 PBD8 756–757 BP8 583
cell carcinomas of the head and neck manifest initially as a
nodal metastasis, without an obvious primary site, but the 3 1 C Pleomorphic adenoma is the most common tumor
microscopic pattern here is not that of squamous cell car- of the parotid gland. These tumors are rarely malignant,
cinoma. Some thyroid cancers initially may manifest as a although they can be locally invasive. An acinic cell tumor is
nodal metastasis, but the microscopic pattern in this case fits composed of cells resembling the serous cells of the salivary
best with paraganglioma. A mucoepidermoid carcinoma or gland; they are generally small, but about one sixth metasta-
a Warthin tumor arises in a salivary gland. size to regional lymph nodes. Mucoepidermoid tumors are
less common than pleomorphic adenomas in major salivary
PBD9 741–742 PBD8 755–756 glands. They may be high-grade and aggressive. Primitive
neuroectodermal tumor, also known as an olfactory neu-
2 8 B The most common cause for dry mouth (xerostomia) roblastoma, is a small, round, blue cell tumor that occurs in
and dry eyes (xerophthalmia) is a medication effect. Anticho- childhood. It is likely to arise in the nasopharyngeal region.
linergics such as trihexyphenidyl to treat the parkinsonian Squamous cell carcinomas arise in the buccal mucosa and
tremor can be implicated, as well as antidepressants, antipsy- are invasive. Warthin tumors are uncommon and indolent,
chotics, and antihistaminics. Alcohol and tobacco use are risks although they may be bilateral or multicentric.
for precancerous lesions and squamous cancers of the oral
cavity. The lack of saliva is unlikely to be associated with infec- PBD9 744–745 BP9 556–557 PBD8 758–759 BP8 584–585
tion, which tends to be focal. Sialadenitis is unlikely to involve
all salivary glands, except in the setting of Sjögren syndrome, 3 2 F Warthin tumor is the second most common salivary
which is associated with SS-A and SS-B autoantibodies, and gland tumor, and it almost always arises within the parotid
may be associated with some pain with inflammation. gland. These tumors tend to be slow growing. Microscopi-
cally there are spaces lined by a double layer of superficial
PBD9 742–743 BP9 555 PBD8 756 BP8 583 columnar and basal cuboidal epithelial cells that are sur-
rounding a lymphoid stroma. Mucoepidermoid carcinomas
29 E Sialadenitis is more common in older individuals, and are infiltrative and form mucous cysts along with a popula-
individuals receiving therapy for schizophrenia with “typi- tion of squamoid cells. Non-Hodgkin lymphoma may arise in
cal” antipsychotics such as haloperidol can have reduced sal- patients with long-standing Sjögren syndrome. Pleomorphic
ivary secretions, which promotes stasis and infection. Most adenomas are more common than Warthin tumors, but have a
neuroleptic drugs are dopamine receptor blockers, but they microscopic appearance with ductal epithelial cells in a myx-
have extrapyramidal and anticholinergic side effects. The oid stroma containing islands of chondroid and bone. Sialo-
dry mouth, coupled with dehydration, favors inspissation of lithiasis is usually accompanied by sialadenitis and is quite
salivary gland secretions and stone formation to block ducts painful. It may produce some gland enlargement, but usually
and increase the risk of inflammation and infection. S. aureus is not a mass effect. Sjögren syndrome can produce some sali-
is the most likely organism to cause infection with suppura- vary gland enlargement, but the process is typically bilateral.
tive inflammation. Epstein-Barr virus can be associated with
hairy leukoplakia. Human papillomavirus infection may lead PBD9 745 BP9 556 PBD8 759 BP8 584–585
to the development of squamous dysplasias and carcinomas.
Prevotella can be found with periodontitis. Rubeola infection 3 3 B Mucoepidermoid carcinomas can arise in major and
with measles can cause Koplik spots at the Stensen duct. minor salivary glands. They account for most neoplasms that
arise within minor salivary glands, particularly malignant
PBD9 743 BP9 555 PBD8 756–757 BP8 583 neoplasms. Low-grade mucoepidermoid carcinomas may
be invasive, but the prognosis is usually good, with a 5-year
30 D The clinical and histologic features suggest a muco- survival of 90%. High-grade mucoepidermoid carcinomas
cele of a minor salivary gland, which is most often the result can metastasize and have a 5-year survival of only 50%. Non-
of local trauma in the very young and very old. There is e ither Hodgkin lymphomas are found in adjacent cervical lymph
rupture or blockage of a salivary gland duct. Chili peppers nodes or in the Waldeyer ring of lymphoid tissue. A primi-
contain capsaicin, which evokes a sensation of tingling and tive neuroectodermal tumor, also known as an olfactory neu-
burning pain by activating a nonselective cation channel, roblastoma, is a small, round, blue cell tumor of childhood; it
called VR1, on vanilloid receptors of sensory nerve endings; is likely to arise in the nasopharyngeal region. Pleomorphic
there is no significant tissue damage. Social behavior may be adenomas are more common in the major salivary glands
a risk factor for infections such as herpes simplex virus. HIV than are mucoepidermoid tumors, and they are more likely
infection is most often associated with oral thrush (candidia- to be indolent. Squamous cell carcinomas are invasive and
sis) and with herpes simplex virus infections. Oral leukoplakia arise in the buccal mucosa. Warthin tumors are uncommon
may appear in various intraoral sites and on the lower lip bor- and indolent.
der, and pipe smoking and tobacco chewing are implicated
in the development of these white patches. Irritation from PBD9 745–746 BP9 557 PBD8 759–760 BP8 584
17C H A P T E R
Gastrointestinal Tract
PBD9 Chapter 17 and PBD8 Chapter 17: The Gastrointestinal Tract
BP9 Chapter 14 and BP8 Chapter 15: Oral Cavity and Gastrointestinal Tract
1 A 23-year-old primigravida gives birth at term to a boy 3 A 23-year-old woman, G2, P1, gave birth at term to a
infant. Ultrasound examination before delivery showed poly- boy of normal weight and length following an uncomplicated
hydramnios. A single umbilical artery is seen at the time of pregnancy. The infant initially did well, but at 6 weeks, he
birth. The infant vomits all feedings, and then develops a fever began feeding poorly for 1 week, and his mother noticed that
and difficulty with respirations within 2 days. A radiograph much of the milk he ingested was forcefully vomited within
shows both lungs and the heart are of normal size, but there 1 hour. Now, on physical examination, the infant is afebrile,
are pulmonary infiltrates and no stomach bubble. What is the and there are no external anomalies. A midabdominal mass is
most likely diagnosis? palpable. Bowel sounds are active. The medical history indi-
A Achalasia cates that both the mother and her first child had the same ill-
B Diaphragmatic hernia ness during infancy. Which of the following conditions is most
C Esophageal atresia likely to explain these findings?
D Hiatal hernia A Annular pancreas
E Pyloric stenosis B Diaphragmatic hernia
F Zenker diverticulum C Duodenal atresia
D Pyloric stenosis
2 A 24-year-old man has developed abdominal pain and E Tracheoesophageal fistula
increasing fatigue over the past 6 months. On physical exami-
nation, he is afebrile and appears pale. On palpation, there is 4 A 24-year-old woman gives birth to term infant after an
mild pain in the right lower quadrant of the abdomen. There uncomplicated pregnancy. Apgar scores are 9 and 10 at 1 and
are no masses, and bowel sounds are active. Laboratory stud- 5 minutes after birth. The infant’s length and weight are at the
ies show hemoglobin, 8.9 g/dL; hematocrit, 26.7%; MCV, 55th percentile. There is no significant passage of meconium.
74 μm3; platelet count, 255,000/mm3; and WBC count, 7780/ Three days after birth, the infant vomits all oral feedings. On
mm3. His stool is positive for occult blood. Upper gastroin- physical examination, the infant is afebrile, but the abdomen
testinal endoscopy and colonoscopy showed no lesions. One is distended and tender, and bowel sounds are reduced. An
month later, he continues to experience the same abdomi- abdominal ultrasound scan shows marked colonic dilation
nal pain. Which of the following is most likely to cause this above a narrow segment in the distal sigmoid region. A biopsy
p atient’s illness? specimen from the narrowed region shows an absence of gan-
A Acute appendicitis glion cells in the muscle wall and submucosa. Which of the
B Angiodysplasia following is most likely to produce these findings?
C Celiac disease A Colonic atresia
D Diverticulosis B Hirschsprung disease
E Giardia lamblia infection C Intussusception
F Meckel diverticulum D Necrotizing enterocolitis
E Trisomy 21
F Volvulus
263
2 6 4 U N I T I I Diseases of Organ Systems 9 A 30-year-old man has sudden onset of hemateme-
sis after a weekend in which he consumed large amounts of
5 A 3-year-old child has attained enough mobility, curios- a lcohol. The bleeding stops, but he has another episode under
ity, and dexterity to explore places in the home that should similar circumstances 1 month later. Upper gastroesophageal
not be accessed. The child finds a bottle with a liquid under endoscopy shows longitudinal tears at the gastroesophageal
the kitchen sink, and he drinks it. Within minutes he has chest junction. What is the most likely mechanism to cause his
pain. His mother takes him to the emergency department, and hematemesis?
brings the bottle. Analysis of the residual contents reveals a A Absent myenteric ganglia
pH of 12. Which of the following complications is most likely B Autoimmune inflammation
to occur following this injury? C Herpes simplex virus infection
A Pharyngeal diverticulum D Portal hypertension
B Esophageal stenosis E Vomiting
C Gastric lymphoma F Widened diaphragmatic crura
D Duodenal ulceration
E Megacolon 10 A 16-year-old boy who is receiving chemotherapy for
acute lymphoblastic leukemia has had pain for 1 week when
6 A 22-year-old woman has had multiple episodes of aspi- he swallows food. Physical examination shows no abnormal
ration of food associated with difficulty swallowing during the findings. Upper gastrointestinal endoscopy shows 0.5- to
past year. On auscultation of her chest, crackles are heard at the 0.8-cm mucosal ulcers in the region of the mid to lower esoph-
base of the right lung. A barium swallow shows marked esoph- agus. The shallow ulcers are round and sharply demarcated,
ageal dilation above the level of the lower esophageal sphincter. and have an erythematous base. Which of the following is
A biopsy specimen from the lower esophagus shows an absence most likely to produce these findings?
of the myenteric ganglia. What is the most likely diagnosis? A Aphthous ulcerations
A Achalasia B Reflux esophagitis
B Barrett esophagus C Herpes simplex esophagitis
C Plummer-Vinson syndrome D Gastroesophageal reflux disease
D Sliding hiatal hernia E Mallory-Weiss syndrome
E Systemic sclerosis
11 A 44-year-old woman has had increasing difficulty
7 A 24-year-old woman living in eastern Bolivia has had swallowing liquids and solids for the past 6 months. On phys-
increasing difficulty with swallowing both liquids and solids ical examination, her fingers have reduced mobility because
for the past year. She has substernal discomfort from a feeling of taut, nondeforming skin. A barium swallow shows marked
that foods “get stuck” going down. On examination her BMI dilation of the esophagus with “beaking” in the distal portion,
is 18. A barium swallow radiologically shows marked esopha- where there is marked luminal narrowing. A biopsy s pecimen
geal dilation. An endoscopic biopsy is obtained and micro- from the lower esophagus shows prominent submucosal
scopically shows reduced ganglion cells in myenteric plexus fibrosis with little inflammation. Which of the following is
along with lymphocytic infiltration. Which of the following most likely to produce these findings?
organisms is most likely infecting this woman? A Barrett esophagus
A Bordetella pertussis B Hiatal hernia
B Candida albicans C Iron deficiency
C Corynebacterium diphtheriae D Portal hypertension
D Herpes simplex virus E Systemic sclerosis
E Trypanosoma cruzi
12 A 57-year-old woman has had burning epigastric
8 A 53-year-old man consumes a very large meal, washed pain after meals for more than 1 year. Physical examination
down with considerable alcohol. The ensuing discomfort shows no abnormal findings. Upper gastrointestinal endos-
prompts him to take an emetic, but soon afterward he devel- copy shows an erythematous patch in the lower esophageal
ops lower chest pain. Physical examination reveals crepitus mucosa. A biopsy specimen shows basal zone squamous epi-
in subcutaneous tissue over his chest along with tachycardia thelial hyperplasia, elongation of lamina propria papillae, and
and tachypnea. Which of the following abnormalities of the scattered intraepithelial neutrophils with some eosinophils.
esophagus is most likely present in this man? Which of the following is the most likely diagnosis?
A Stricture A Barrett esophagus
B Achalasia B Esophageal varices
C Ectopia C Iron deficiency
D Rupture D Reflux esophagitis
E Varices E Systemic sclerosis
C H A P T E R 1 7 Gastrointestinal Tract 2 6 5
13 A 51-year-old man has sudden onset of massive emesis
of bright red blood. On physical examination, his tempera-
ture is 36.9° C, pulse is 103/min, respirations are 23/min, and
blood pressure is 85/50 mm Hg. His spleen tip is palpable.
Laboratory studies show a hematocrit of 21%. The serologic
test result for HBsAg is positive. He has had no prior episodes
of hematemesis. The hematemesis is most likely to be a conse-
quence of which of the following?
A Barrett esophagus
B Candida albicans infection
C Esophageal varices
D Reflux esophagitis
E Squamous cell carcinoma
F Zenker diverticulum
14 A 55-year-old man has had increasing difficulty swal- 16 A 73-year-old man with a history of chronic alcoholism
lowing during the past 6 months. There are no significant has had increasing difficulty swallowing and has noticed a
findings on physical examination. Upper gastrointestinal 3-kg weight loss over the past 2 months. On physical examina-
endoscopy shows areas of erythematous mucosa 3 cm above tion, there are no remarkable findings. Upper gastrointestinal
the Z-line. A biopsy specimen from the lower esophagus has endoscopy shows a 3-cm ulcerative mass in the midesophagus
changes in the mucosal epithelium illustrated in the figure. that partially occludes the esophageal lumen. Esophagectomy
Which of the following complications is most likely to occur as is performed; the gross appearance of the lesion is shown in
a consequence of this patient’s condition? the figure. Which of the following is most likely to be seen on
A Achalasia microscopic section of this mass?
B Adenocarcinoma A Adenocarcinoma
C Diverticular formation B Dense collagenous scar
D Lacerations (Mallory-Weiss syndrome) C Dilated vascular channels
E Squamous cell carcinoma D Multinucleated cells with intranuclear inclusions
E Squamous cell carcinoma
15 A 68-year-old man from Birmingham, England, has had
“heartburn” and substernal pain after meals for 25 years. For 17 A 66-year-old man living in Tehran, Iran, has been
the past year, he has had increased pain with difficulty swal- bothered by difficulty swallowing for the past year. He is
lowing both liquids and solids. On physical examination, there now consuming liquid food. Yesterday he regurgitated food
are no remarkable findings. Upper gastrointestinal endoscopy stained with blood. On esophagoscopy, there is an ulcerated
shows an ulcerated lower esophageal mass that nearly occludes obstructing lesion 20 cm from the lips. Biopsies are taken and
the lumen of the esophagus. A biopsy specimen of this mass is on microscopy show infiltrating nests of keratinized cells with
most likely to show which of the following neoplasms? distinct cell borders and hyperchromatic, angulated nuclei.
A Adenocarcinoma Which of the following is the most likely risk factor for his
B Carcinoid tumor disease?
C Leiomyosarcoma A Genetic susceptibility
D Non-Hodgkin lymphoma B Autoimmunity
E Squamous cell carcinoma C Diet
D Infection
E Reflux
2 6 6 U N I T I I Diseases of Organ Systems 22 A 59-year-old man has had nausea and vomiting for
5 months. He has experienced no hematemesis. On physical
18 A 38-year-old woman has had nausea for 6 months. examination, there is no abdominal tenderness, and bowel
She reports no vomiting or diarrhea. On physical examina- sounds are present. Upper gastrointestinal endoscopy shows
tion, there are no remarkable findings. Upper gastrointestinal erythematous areas of mucosa with thickening of the rugal
endoscopy shows diffuse gastric mucosal erythema with focal folds in the gastric antrum. The microscopic appearance of a
mucosal erosions, but no ulcerations. The esophageal and gastric biopsy specimen with a Steiner silver stain is shown
duodenal mucosal surfaces appear normal. Gastric biopsies in the figure. Which of the following factors is most likely
are obtained and microscopic examination shows focal muco- responsible for this gastric mucosal pathology?
sal hemorrhage, loss of the surface epithelium, and increased A Cysteine proteinase
numbers of neutrophils, lymphocytes, and plasma cells in an B Cytotoxin-associated gene A
edematous mucosa. No Helicobacter pylori organisms are seen. C Heat-stable enterotoxin
Laboratory studies show a normal serum gastrin level. Which D Shiga toxin
of the following pharmacologic agents is most likely to pro- E Verocytotoxin
duce these findings?
A Aspirin 23 A 47-year-old woman with a lengthy history of heart-
B Chlorpromazine burn and dyspepsia experiences sudden onset of abdominal
C Cimetidine pain. On physical examination, she has severe mid epigastric
D Clindamycin pain with guarding. Bowel sounds are reduced. An abdomi-
E Omeprazole nal plain film radiograph shows free air under the left leaf of
the diaphragm. She is immediately taken to surgery, and a
19 A 72-year-old man takes large quantities of nonsteroidal perforated duodenal ulcer is repaired. Which of the following
anti-inflammatory drugs (NSAIDs) because of chronic degen- organisms is most likely to have produced these findings?
erative arthritis of the hips and knees. Over the past 2 weeks, A Campylobacter jejuni
he has had epigastric pain with nausea and vomiting and an B Cryptosporidium parvum
episode of hematemesis. On physical examination, there are C Giardia lamblia
no remarkable findings. A gastric biopsy specimen is most D Helicobacter pylori
likely to show which of the following lesions? E Salmonella typhi
A Acute gastritis F Shigella flexneri
B Adenocarcinoma G Yersinia enterocolitica
C Epithelial dysplasia
D Helicobacter pylori infection 24 A 35-year-old man has had epigastric pain for more than
E Hyperplastic polyp 1 year. The pain tends to occur 2 to 3 hours after a meal and is
relieved if he takes antacids or eats more food. He has noticed
20 A 54-year-old, previously healthy man sustained an a 4-kg weight gain in the past year. He does not smoke and
extensive thermal burn injury involving 70% of the total body drinks 1 glass of Johannisberg Riesling daily. The result of a
surface area of his skin. He was hospitalized in stable condi- urea breath test is positive, and a gastric biopsy specimen con-
tion. Three weeks after the initial burn injury, he developed tains urease. He begins a 2-week course of antibiotics, but on
melanotic stools. His blood pressure dropped to 80/40 mm day 4, he feels better and discontinues treatment. Three weeks
Hg, and his hematocrit declined to 18%. Where are gastroin- later, the epigastric pain recurs. If he does not seek further
testinal ulcerations most likely to be found in this man? treatment, which of the following complications is he most
A Colon likely to develop?
B Duodenum A Carcinoid syndrome
C Esophagus B Fat malabsorption
D Ileum C Hematemesis
E Stomach D Migratory thrombophlebitis
E Vitamin B12 deficiency
21 A 51-year-old woman has been feeling increasingly
tired for the past 7 months. There are no remarkable findings
on physical examination. Laboratory studies include hemo-
globin, 9.5 g/dL; hematocrit, 29.1%; MCV, 124 μm3; platelet
count, 268,000/mm3; and WBC count, 8350/mm3. The retic-
ulocyte index is low. Hypersegmented polymorphonuclear
leukocytes are found on a peripheral blood smear. The serum
gastrin is markedly increased. Antibodies to which of the fol-
lowing are most likely to be found in this patient?
A Gastric H+,K+-ATPase
B Gliadin
C Helicobacter pylori
D Intrinsic factor receptor
E Tropheryma whippelli
25 A 52-year-old man notes nausea with abdominal dis- C H A P T E R 1 7 Gastrointestinal Tract 2 6 7
comfort after meals. On physical examination, there are no specimen shows a monomorphous infiltrate of lymphoid cells
abnormal findings. Upper endoscopy is performed, and there microscopically. Helicobacter pylori organisms are identified
are three ovoid nodules in the fundus and antrum ranging in mucus overlying adjacent mucosa. Cytogenetic analysis
from 0.3 to 1.2 cm in size. They have rounded, smooth sur- shows t(11;18)(q21;q21). He receives antibiotic therapy for
faces. Biopsies are taken and on microscopic examination H. pylori, and the repeat biopsy specimen shows a resolution
there are irregular, cystically dilated and elongated foveolar of the infiltrate. What is the most likely diagnosis?
glands. Which of the following treatment strategies is most A Autoimmune gastritis
appropriate for his gastric lesions? B Chronic gastritis
A Antibiotics C Crohn disease
B Chemotherapy D Diffuse large B-cell lymphoma
C Corticosteroids E Gastrointestinal stromal tumor
D Multivitamins F Mucosa-associated lymphoid tissue tumor
E Total gastrectomy
F Vagotomy
30 A 26-year-old man is brought to the emergency depart-
26 A 49-year-old woman has a history of peptic ulcer disease ment after sustaining abdominal gunshot injuries. At laparotomy,
for which she has been treated with proton pump inhibitors. She while repairing the small intestine, the surgeon notices a 1-cm
has had nausea with vomiting for the past 2 months. Upper GI mass at the tip of the appendix. The yellow-tan submucosal mass
endoscopy reveals three circumscribed, round, smooth lesions is removed, and the microscopic appearance of the mass is shown
in the gastric body from 1 to 2 cm in diameter. Biopsies are taken in the figure. Immunohistochemical staining is positive for chro-
and microscopically show the lesions to consist of irregular mogranin and synaptophysin but negative for Ki-67. Which of
glands that are cystically dilated and lined by flattened parietal the following is the most likely cell of origin of this lesion?
and chief cells. No inflammation, Helicobacter pylori, metaplasia, A Lipoblast
or dysplasia is present. What is the most likely diagnosis? B Ganglion cell
C Goblet cell
A Fundic gland polyps D Neuroendocrine cell
B Gastric adenomas E Smooth muscle cell
C Hyperplastic polyps 31 A 55-year-old man experiences episodes of diaphoresis,
D Hypertrophic gastropathy dyspnea, and diarrhea for 10 months. On physical examina-
tion he has midabdominal discomfort with deep palpation,
27 A 53-year-old woman has had nausea, vomiting, and and bowel sounds are reduced. There are no abnormal find-
midepigastric pain for 5 months. On physical examination, there ings with upper endoscopy. Abdominal CT scan shows three
are no significant findings. An abdominal CT scan shows gastric nodules in the liver, from 1 to 3 cm in size. Laboratory stud-
outlet obstruction. Upper gastrointestinal endoscopy shows an ies show a high level of serum 5-hydroxyindoleacetic acid
ulcerated 2 × 4 cm bulky mass in the antrum at the pylorus. A (5-HIAA). Camera endoscopy is performed, and on review of
urease test is positive. Which of the following neoplasms is most the images, there is a midjejunal mass that partially obstructs
likely to be seen in a biopsy specimen of this mass? the lumen. At laparotomy a 5-cm submucosal jejunal mass is
A Adenocarcinoma resected, and on microscopy it is composed of nests and tra-
B Leiomyosarcoma beculae of round cells with pink, granular cytoplasm. The cells
C Neuroendocrine carcinoma of this mass are most likely related to which of the following
D Non-Hodgkin lymphoma embryologic derivatives?
E Squamous cell carcinoma A Endoderm
B Ectoderm
28 A 67-year-old woman has experienced severe nausea, C Neural crest
vomiting, early satiety, and a 9-kg weight loss over the past D Notochord
4 months. On physical examination, she has muscle wasting. E Splanchnic mesoderm
Upper gastrointestinal endoscopy shows that the entire gas-
tric mucosa is eroded and has an erythematous, cobblestone
appearance. An abdominal CT scan shows that the stomach is
small and shrunken. Which of the following is most likely to be
found on histologic examination of a gastric biopsy specimen?
A Chronic atrophic gastritis
B Primary gastric lymphoma
C Gastrointestinal stromal tumor
D Granulomatous inflammation
E Signet ring cell adenocarcinoma
29 A 52-year-old man has had a 4-kg weight loss and nau-
sea for the past 6 months. He has no vomiting or diarrhea.
On physical examination, there are no remarkable findings.
Upper gastrointestinal endoscopy shows a 6-cm area of irreg-
ular, pale fundic mucosa and loss of the rugal folds. A biopsy
2 6 8 U N I T I I Diseases of Organ Systems 35 A 61-year-old man has had severe abdominal pain and
bloody diarrhea for the past day. On physical examination, his
32 A 61-year-old man with increasing fatigue, early satiety, abdomen is diffusely tender, and bowel sounds are absent.
and nausea for 5 months vomited dark granular material yes- Abdominal plain films show no free air. Laboratory studies
terday. Endoscopy reveals a large ulcerated mass in the gas- show a normal CBC and normal levels of serum amylase,
tric fundus. Biopsies are taken and microscopically the mass lipase, and bilirubin. His Hgb A1c is 10%. He develops shock.
is composed of spindle cells that are positive for c-Kit with A year ago he had an acute myocardial infarction. Which of
immunohistochemical staining. Mitoses are frequent. Gastrec- the following lesions is most likely to be found in this man?
tomy is performed, and the 10-cm circumscribed mass arises A Appendicitis
from the gastric wall. Which of the following therapies is most B Cholecystitis
likely to be a useful adjunct in treatment of his disease? C Pancreatitis
A Amoxicillin D Intestinal infarction
B Azathioprine E Pseudomembranous colitis
C Cyclophosphamide
D Imatinib 36 A 71-year-old woman with a history of rheumatic heart
E Prednisone disease is hospitalized with severe congestive heart failure.
F Radiation Four days after admission, she develops cramping lower
a bdominal pain. On physical examination, she is afebrile. The
33 A 57-year-old man from Innsbruck, Austria, goes to the abdomen is distended and tympanitic, without a fluid wave,
emergency department because of increasing abdominal pain and bowel sounds are absent. A stool sample is positive for
with distention that developed over the past 24 hours. On occult blood. An abdominal plain film shows no free air.
physical examination, there is diffuse abdominal tenderness. Colonoscopy shows patchy areas of mucosal erythema with
The abdomen is tympanitic, without a fluid wave, and bowel some overlying tan exudate in the ascending and descending
sounds are nearly absent. There is a well-healed, 5-cm trans- colon. No polyps or masses are found. What is the most likely
verse scar in the right lower quadrant of the abdomen. There is diagnosis?
no caput medusa. A stool sample is negative for occult blood. A Ischemic colitis
An abdominal plain film shows dilated loops of small bowel B Mesenteric vasculitis
with air-fluid levels, but there is no free air. At laparotomy, C Shigellosis
the surgeon notices a 20-cm portion of reddish black ileum D Ulcerative colitis
that changes abruptly to pink-appearing bowel on distal and E Volvulus
proximal margins. His medical history is significant only for
an appendectomy at age 25 years. Which of the following is 37 A 60-year-old man has had increasing fatigue for the
most likely to have produced his findings? past 8 months. On physical examination, he appears pale. On
A Adenocarcinoma of the ileum digital rectal examination, no masses are palpable, but a stool
B Adhesions sample is positive for occult blood. Auscultation of the abdo-
C Crohn disease men shows active bowel sounds, and on palpation there are
D Indirect inguinal hernia no masses or areas of tenderness. Laboratory studies show
E Intussusception hemoglobin, 8.3 g/dL; hematocrit, 24.6%; MCV, 73 μm3; plate-
F Tuberculosis let count, 226,000/mm3; and WBC count, 7640/mm3. Colo-
G Volvulus noscopy shows no identifiable source of the bleeding. Angi-
ography shows a 1-cm focus of dilated and tortuous vascular
34 An 11-month-old, previously healthy infant has not pro- channels in the mucosa and submucosa of the cecum. What is
duced a stool for 1 day. The mother notices that the infant’s the most likely diagnosis?
a bdomen is distended. On physical examination, the infant’s A Angiodysplasia
abdomen is very tender, and bowel sounds are nearly absent. B Collagenous colitis
An abdominal plain film radiograph shows no free air, but C Diverticulosis
there are distended loops of small bowel with air-fluid levels. D Internal hemorrhoids
Which of the following is most likely to produce these findings? E Mesenteric vein thrombosis
A Duodenal atresia
B Hirschsprung disease 38 A 21-year-old man has had increasingly voluminous,
C Intussusception bulky, foul-smelling stools and a 7-kg weight loss for the past
D Meckel diverticulum year. There is no history of hematemesis or melena. He has
E Pyloric stenosis some bloating, but no abdominal pain. On physical exami-
nation, there are no palpable abdominal masses, and bowel
sounds are present. Which of the following laboratory find-
ings is most likely to be present on examination of his stool?
A Entamoeba histolytica trophozoites
B Giardia lamblia cysts
C Increased stool fat
D Occult blood
E Vibrio cholerae organisms
39 A 34-year-old woman is bothered by a low-volume, C H A P T E R 1 7 Gastrointestinal Tract 2 6 9
mostly watery diarrhea associated with flatulence. The symp-
toms occur episodically, but they have been persistent for the 43 A potluck lunch party is held at the office at noon. Vari-
past year. She has experienced a 4-kg weight loss. She has ous meats, salads, breads, and desserts that were brought in
no fever, nausea, vomiting, or abdominal pain. On physical earlier that morning are served. Everyone has a good time,
e xamination, there are no significant findings. A stool sample and most of the food is consumed. By midafternoon, the
is negative for occult blood, ova, and parasites, and a stool single office restroom is being used by many employees who
culture yields no pathogens. An upper gastrointestinal endos- have vomiting and acute, explosive diarrhea accompanied by
copy is performed and a biopsy specimen from the upper part abdominal cramping. Which of the following infectious agents
of the small bowel shows severe diffuse blunting of villi and is most likely responsible for this turn of events?
a chronic inflammatory infiltrate in the lamina propria. Which A Bacillus cereus
of the following serologic tests is most likely to be positive in B Clostridium difficile
this patient? C Escherichia coli
A Anticentromere antibody D Salmonella enterica
B Anti–DNA topoisomerase I antibody E Staphylococcus aureus
C Antimitochondrial antibody F Vibrio parahaemolyticus
D Antinuclear antibody
E Antitransglutaminase antibody 44 A healthy 21-year-old woman develops a profuse, watery
diarrhea 1 day after a meal of raw oysters. On physical exami-
40 A 41-year-old woman has had diarrhea and fatigue with nation, her temperature is 37.5° C. A stool sample is negative
a 3-kg weight loss over the past 6 months. On physical exami- for occult blood. There is no abdominal distention or tender-
nation, she is afebrile and has mild muscle wasting, but her ness, and bowel sounds are present. The diarrhea subsides
motor strength is normal. Laboratory studies show no occult over the next 3 days. Which of the following organisms is most
blood, ova, or parasites in the stool. A biopsy specimen from likely to produce these findings?
the upper jejunum is obtained, and microscopic findings are A Cryptosporidium parvum
reviewed. The patient begins following a special diet with no B Entamoeba histolytica
wheat or rye grain products. The change in diet produces dra- C Staphylococcus aureus
matic improvement. Which of the following microscopic fea- D Vibrio parahaemolyticus
tures is most likely to be seen in the biopsy specimen? E Yersinia enterocolitica
A Crypt abscesses and mucosal ulceration
B Foamy macrophages within the lamina propria 45 A 26-year-old man traveling to Ching Mai, Thailand,
C Lymphatic obstruction had fever, headache, and muscle pains for a day followed by
D Noncaseating granulomas watery diarrhea of 5 to 10 stools per day for 4 days. In the
E Villous blunting and flattening past day, the diarrhea has been bloody and accompanied by
tenesmus. On physical examination there is diffuse abdominal
41 An epidemiologic study of children with failure to pain. Microscopic examination of the stool shows numerous
thrive is undertaken in Guatemala. Some of these children leukocytes and gram-negative curved rods. The diarrhea sub-
with ages 1 to 3 years have repeated bouts of diarrhea, but sides, but 2 weeks later he has increasing weakness in his legs.
do not improve with dietary supplements. Jejunal biopsies Which of the following organisms is most likely to produce his
show blunted, atrophic villi with crypt elongation and chronic disease?
inflammatory infiltrates. What is the most likely factor contrib- A Bacillus cereus
uting to recurrent diarrhea in these children? B Campylobacter jejuni
A Abetalipoproteinemia C Clostridium perfringens
B Bacterial infection D Giardia lamblia
C Chloride ion channel dysfunction E Rotavirus
D Disaccharidase deficiency
E NOD2 gene mutations 46 A 36-year-old man experiences cramping abdomi-
nal pain with fever and watery diarrhea 2 days after eating
42 A 40-year-old man has episodic abdominal bloating, a chicken salad sandwich. Physical examination shows mild
flatulence, and explosive diarrhea. These symptoms appear diffuse abdominal pain on palpation, but there are no masses.
to be related to the milk shakes that he loves to consume. Bowel sounds are present. A stool sample is negative for
On physical examination, there are no remarkable findings. occult blood. He recovers completely within 5 days without
Laboratory studies show no increase in stool fat and no occult treatment. Which of the following infectious organisms is
blood, ova, or parasites in the stool. A routine stool culture most likely to produce these findings?
yields no pathogens. When he does not consume milk shakes A Bacillus cereus
or ice cream sodas, he is not symptomatic. Which of the fol- B Entamoeba histolytica
lowing conditions best accounts for these findings? C Escherichia coli
A Autoimmune gastritis D Rotavirus
B Celiac disease E Salmonella enterica
C Cholelithiasis F Staphylococcus aureus
D Cystic fibrosis G Yersinia enterocolitica
E Disaccharidase deficiency
2 7 0 U N I T I I Diseases of Organ Systems 49 Over a holiday weekend, more than 100 adults at a
47 In an epidemiologic study of infections of the gastro- resort hotel develop a diarrheal illness marked by volumi-
intestinal tract, cases of patients living in Haiti from whom nous, w atery stools more than 10 times per day. They also
definitive cultures were obtained are analyzed for clinical report headache, abdominal cramping pain, and myalgias. On
and pathologic findings that may be useful for diagnosis. A physical examination they have manifestations of dehydration
group of patients is identified who initially had abdominal and mild fever. Laboratory studies of stool samples show no
pain and diarrhea during week 1 of their illness. By week 2, increase in leukocytes or fat, and no RBCs. Their illness lasts
these patients had splenomegaly and elevations in serum AST just 1 to 3 days and resolves with no sequelae. Which of the
and ALT levels. By week 3, they were septic and had leuko- following infectious agents is the most likely cause for their
penia. At autopsy, the patients who died were found to have illness?
ulceration of Peyer patches. Which of the following infectious A Cytomegalovirus
agents is most likely to produce these findings? B Clostridium botulinum
A Campylobacter jejuni C Norovirus
B Clostridium perfringens D Staphylococcus aureus
C Mycobacterium bovis E Strongyloides stercoralis
D Salmonella typhi F Vibrio cholerae
E Shigella sonnei
F Yersinia enterocolitica 50 A 5-month-old, previously healthy infant girl in Ban-
gladesh develops a watery diarrhea that lasts for 1 week. The
infant has a mild fever during the illness, but has no abdomi-
48 A 65-year-old woman is being treated in the hospital nal pain or swelling. On physical examination, her tempera-
for pneumonia complicated by septicemia. She has required ture is 37.7° C. A stool sample is negative for occult blood, ova,
multiple antibiotics and was intubated and mechanically ven- or parasites. Her parents are told to give her plenty of fluids,
tilated earlier in the course. On day 20 of hospitalization, she and she recovers fully. Which of the following organisms is
has abdominal distention. Bowel sounds are absent, and an most likely to produce these findings?
abdominal radiograph shows dilated loops of small bowel A Campylobacter jejuni
suggestive of ileus. She has a low volume of bloody stool that is B Cryptosporidium parvum
positive for Clostridium difficile toxin. Laboratory studies show C Escherichia coli
leukocytosis and hypoalbuminemia. At laparotomy, a portion D Listeria monocytogenes
of distal ileum and cecum is resected. The gross a ppearance of E Norwalk virus
the mucosal surface is shown in the figure. What is the most F Rotavirus
likely diagnosis? G Shigella flexneri
A Gas gangrene with myonecrosis
B Inflammatory bowel disease 51 A study of children living in rural Malawi in Africa
C Ischemic bowel disease reveals a high prevalence of iron deficiency anemia. Stool
D Pseudomembranous enterocolitis samples are positive for occult blood. Pruritus of the skin of
E Toxic megacolon their feet as well as cough are additional findings in many of
these children. Which of the following parasitic infestations is
the most likely cause for these findings?
A Ancylostoma duodenale
B Ascaris lumbricoides
C Cryptosporidium parvum
D Enterobius vermicularis
E Schistosoma mansoni
52 A 31-year-old woman had increasingly severe diarrhea
1 week after returning from a trip to Central America. Gross
examination of the stools showed mucus and streaks of blood.
The diarrheal illness subsided within 4 weeks, but now she
has become febrile and has pain in the right upper quadrant of
the abdomen. An abdominal ultrasound scan shows a 10-cm,
irregular, partly cystic mass in the right hepatic lobe. Which of
the following infectious organisms is most likely to produce
these findings?
A Clostridium difficile
B Cryptosporidium parvum
C Giardia lamblia
D Entamoeba histolytica
E Strongyloides stercoralis
C H A P T E R 1 7 Gastrointestinal Tract 271
A Cystic fibrosis
B Diverticular disease
C Inflammatory bowel disease
D Irritable bowel syndrome
E Viral gastroenteritis
53 A 27-year-old man has sudden onset of marked abdomi- 55 A 49-year-old woman has had abdominal cramps and
nal pain. On physical examination, his abdomen is diffusely diarrhea with six stools per day for the past month. She has a
tender and distended, and bowel sounds are absent. He history of similar episodes of self-limited pain and diarrhea,
undergoes surgery, and a 27-cm segment of terminal ileum which have occurred multiple times during the past 20 years.
with a firm, erythematous serosal surface is removed. The Each episode lasts about 2 weeks and resolves without treat-
microscopic appearance of a section through the excised ileum ment. Findings on physical examination are unremarkable, but
is shown in the figure. Which of the following additional com- a stool sample is positive for occult blood. Laboratory studies
plications is the patient most likely to develop as a result of show no ova or parasites in the stool. Colonoscopy shows dif-
this disease process? fuse and uninterrupted mucosal inflammation and superficial
A Adenocarcinoma ulceration extending from the rectum to the ascending colon.
B Enterocutaneous fistula Colonic biopsy specimens from the area show the findings in
C Intussusception the figure. She is at greatest risk for developing which of the
D Liver abscess following complications?
E Mesenteric artery thrombosis A Adenocarcinoma
B Diverticulitis
54 A 30-year-old woman has a 5-year history of recurrent C Fat malabsorption
episodes marked by days of abdominal bloating with alternat- D Perirectal fistula formation
ing constipation and diarrhea. She notes hard stools of nar- E Primary biliary cirrhosis
row caliber, low volume mucous diarrhea, and pain in the left F Pseudomembranous colitis
lower quadrant. Her symptoms are relieved by defecation,
which occurs more frequently now. On physical examination
there are no abnormal findings. Laboratory studies including
stool for ova and parasites, bacterial pathogens, and fat show
no abnormalities. An abdominal CT scan is unremarkable.
What is the most likely diagnosis?
2 7 2 U N I T I I Diseases of Organ Systems 58 A 26-year-old man has had intermittent cramping
abdominal pain and low-volume diarrhea for 3 weeks. On
56 A 35-year-old woman has had increasing lower back physical examination, he is afebrile; there is mild lower
pain for 5 years. During the past year she also has had arthritic abdominal tenderness but no masses, and bowel sounds are
pain involving the knees, hips, and wrists. A stool sample is present. A stool sample is positive for occult blood. The symp-
positive for occult blood. A pelvic radiograph shows changes toms subside within 1 week. Six months later, the abdominal
consistent with sacroiliitis. A colonoscopy is performed, and pain recurs with perianal pain. On physical examination, there
she undergoes a total colectomy. The figure shows the gross is now a perirectal fistula. Colonoscopy shows many areas of
appearance of the colectomy specimen. What is the most likely mucosal edema and ulceration and some areas that appear
underlying mechanism of the illustrated condition? normal. Microscopic examination of a biopsy specimen from
A Development of autoantibodies directed against an ulcerated area shows a patchy acute and chronic inflam-
matory infiltrate, crypt abscesses, and noncaseating granulo-
tropomyosin mas. Which of the following underlying disease processes best
B Development of antimicrobial antibodies that cross explains these findings?
A Amebiasis
react with colonic mucosa B Crohn disease
C Development of TH17 immune responses C Sarcoidosis
D Germline inheritance of the APC gene mutation D Shigellosis
E Mutations in the NOD2 gene E Ulcerative colitis
57 A 30-year-old woman has suffered intermittent bouts of
lower abdominal pain and low-volume diarrhea for the past 59 A clinical study of adult patients with chronic bloody
2 years. On colonoscopy there is friable mucosa from the rec- diarrhea is performed. One group of these patients is found
tum to the ascending colon, and a perianal fistula is noted. Biop- to have a statistically increased likelihood for the following:
sies are taken and on microscopic examination show acute and antibodies to Saccharomyces cerevisiae but not anti–neutrophil
chronic mucosal inflammation with focal erosion. Her stool is cytoplasmic autoantibodies, NOD2 gene polymorphisms, TH1
negative for ova, parasites, and bacterial pathogens. Which of and TH17 immune cell activation, vitamin K deficiency, mega-
the following ongoing testing procedures is most useful for loblastic anemia, and gallstones. Which of the following dis-
long-term follow-up of this woman? eases is this group of patients most likely to have?
A Abdominal CT scanning A Angiodysplasia
B Biopsy screening for dysplasia B Crohn disease
C Genetic mutational analysis for NOD2 C Diverticulitis
D Serologic titers for Saccharomyces D Ischemic enteritis
E Stool cultures for microbiota E Ulcerative colitis
60 A 65-year-old woman has a routine health maintenance
examination. A stool sample is positive for occult blood.
CT scan of the abdomen shows numerous air-filled, 1-cm out-
pouchings of the sigmoid and descending colon. Which of
the following complications is most likely to develop in this
patient?
A Adenocarcinoma
B Bowel obstruction
C Pericolic abscess
D Malabsorption
E Toxic megacolon
61 The mother of a 4-year-old child notes blood when laun-
dering his underwear. Physical examination reveals a rectal
mass. On proctoscopy, there is a smooth-surfaced, peduncu-
lated, 1.5-cm polyp. It is excised and microscopically shows
cystically dilated crypts filled with mucin and inflammatory
debris, but no dysplasia. What is the most likely diagnosis?
A Familial adenomatous polyposis
B Gardner syndrome
C Juvenile polyp
D Lynch syndrome
E Peutz-Jeghers syndrome
C H A P T E R 1 7 Gastrointestinal Tract 2 7 3
A
B 63 A 70-year-old man has a routine health maintenance
examination. On physical examination, there are no remark-
62 A 53-year-old woman undergoes a routine checkup. able findings, but a stool sample is positive for occult blood.
The only abnormal finding is a stool specimen that contains A colonoscopy is performed and shows a 5-cm sessile mass in
o ccult blood. Colonoscopy shows a 1.5-cm, solitary, rounded, the upper portion of the descending colon at 50 cm from the
erythematous polyp on a 0.5-cm stalk at the splenic flexure. anal verge. The histologic appearance at low power of a biopsy
The polyp is removed; its histologic appearance is shown in specimen of the lesion is shown in the figure. The patient
the figure at low (A) and high (B) magnifications. Her colonic refused further workup and treatment. Five years later, he has
lesion is most likely associated with which of the following? constipation, microcytic anemia, and a 5-kg weight loss over
A Low risk for development of carcinoma 6 months. On surgical exploration, there is a 7-cm mass encir-
B Inheritance of an abnormal tumor suppressor gene cling the descending colon. Which of the following neoplasms
C Presence of similar lesions in the small intestine is he now most likely to have?
D History of iron deficiency anemia A Adenocarcinoma
E Risk for development of endometrial carcinoma B Non-Hodgkin lymphoma
C Carcinoid tumor
D Leiomyosarcoma
E Mucinous cystadenoma
F Villous adenoma
2 7 4 U N I T I I Diseases of Organ Systems
64 A 19-year-old man is advised to see his physician b ecause 66 A 33-year-old man has a routine health maintenance
genetic screening has detected a disease in other family mem- e xamination. A stool sample is positive for occult blood. On
bers. On physical examination, a stool sample is positive for colonoscopy, a 6-cm ulcerative lesion is seen projecting into
occult blood. A colonoscopy is performed, followed by a col- the cecum. There are three smaller sessile lesions from 1 to
ectomy. The figure shows the gross appearance of the mucosal 3 cm in size. The microscopic appearance of a section of the
surface of the colectomy specimen. Microscopic examination ulcerated lesion is shown in the figure. The smaller lesions are
shows these lesions are tubular adenomas. Molecular analy- reported as sessile serrated adenomas. Which of the following
sis of this patient’s normal fibroblasts is most likely to show a molecular biological events is thought to be most c ritical in the
m utation in which of the following genes? development of such lesions?
A APC A Amplification of ERBB2 gene
B MLH1 B Defective DNA mismatch repair gene
C KRAS C Germline transmission of a defective RB1 gene
D NOD2 D Overexpression of E-cadherin gene
E p53 E Translocation of retinoic acid receptor alpha gene
65 A 44-year-old woman has had increasing abdominal dis-
tention for the past 6 weeks. On physical examination, there is 67 A 73-year-old man has noted a change in bowel habits
an abdominal fluid wave, and bowel sounds are present. Para- for the past year. Defecation is more difficult and the caliber
centesis yields 1000 mL of slightly cloudy serous fluid. Cyto- of stools has decreased. On physical exam, there are no abnor-
logic examination of the fluid shows malignant cells consistent mal findings except for stool positive for occult blood. Colo-
with adenocarcinoma. Molecular analysis of these cells shows noscopy is performed for the first time in this man, followed
an MSH2 gene mutation with microsatellite instability. Her by colonic resection with the gross appearance shown in the
medical history indicates that she has had no major medical figure. Which of the following molecular abnormalities has
illnesses and no surgical procedures. Her sister was diagnosed most likely led to these findings?
with endometrial cancer and her brother had carcinoma of the A Acquired APC gene mutation
stomach. Which of the following conditions is the most likely B Homozygous loss of PTEN gene
cause of this patient’s symptoms? C Inactivation of the RB1 protein by HPV-16
A Angiodysplasia D Mutation in a DNA mismatch repair gene
B Crohn disease E Tyrosine kinase activation with KIT mutation
C Diverticulosis
D Lynch syndrome
E Peptic ulcer disease
68 A 20-year-old woman in her ninth month of pregnancy C H A P T E R 1 7 Gastrointestinal Tract 2 7 5
has increasing pain on defecation and notices bright red blood
on the toilet paper. She has had no previous gastrointestinal 70 A 53-year-old woman has increasing abdominal girth
problems. After she gives birth, the rectal pain subsides, and for the past 2 years. On physical examination she has abdomi-
there is no more bleeding. Which of the following is the most nal distension. An abdominal CT scan shows multiple nodules
likely cause of these findings? on peritoneal surfaces along with low attenuation mucinous
A Angiodysplasia ascites. Paracentesis is performed and cytologic examination
B Hemorrhoids of the fluid obtained shows well-differentiated columnar cells
C Intussusception with minimal nuclear atypia. Where did this proliferative
D Ischemic colitis process most likely arise in this woman?
E Volvulus A Appendix
B Jejunum
69 A 20-year-old woman has had nausea and vague lower C Ileum
abdominal pain for the past 24 hours, but now the pain has D Pancreas
become more severe. On physical examination, the pain is E Stomach
worse in the right lower quadrant, and there is rebound tender- 71 A 59-year-old man with a lengthy history of chronic
ness. A stool sample is negative for occult blood. Abdominal alcoholism has noticed increasing abdominal girth for the past
plain film radiographs show no free air. The result of a serum 6 months. He has had increasing abdominal pain for the past
pregnancy test is negative. Which of the following laboratory 2 days. On physical examination, his temperature is 38.2° C.
findings is most useful to aid in the diagnosis of this patient? Examination of the abdomen shows a fluid wave and promi-
A Entamoeba histolytica cysts in the stool nent caput medusae over the skin of the abdomen. There is
B Hyperamylasemia diffuse abdominal tenderness. An abdominal plain film radio-
C Hypernatremia graph shows no free air. Paracentesis yields 500 mL of cloudy
D Increased serum alkaline phosphatase yellow fluid. Gram stain of the fluid shows gram-negative
E Increased serum carcinoembryonic antigen rods. Which of the following is the most likely diagnosis?
F Neutrophilia with left shift A Appendicitis
B Collagenous colitis
C Diverticulitis
D Ischemic colitis
E Pseudomembranous colitis
F Spontaneous bacterial peritonitis
ANSWERS may be difficult to detect, and it is almost always seen in
patients older than 70 years, but can cause significant blood
1 C An esophageal atresia is often combined with a fistula loss. Celiac disease can occur in young individuals, but it
between the esophagus and trachea. Gastrointestinal obstruc- does not produce significant hemorrhage. Diverticulosis can
tion in utero can lead to polyhydramnios. The presence of a be associated with hemorrhage, but the diverticula are almost
single umbilical artery suggests additional anomalies are pres- always in the colon of older persons. Giardiasis produces a
ent. Vomiting in an infant risks aspiration with development self-limited, watery diarrhea without hemorrhage.
of pneumonia. Achalasia is incomplete relaxation of the lower
esophageal sphincter and is usually not manifested at birth. PBD9 751 PBD8 765–766 BP8 600
Absence of a diaphragmatic leaf, usually on the left, results in
herniation of abdominal contents into the chest and functional 3 D The infant’s condition occurred several weeks after
gastrointestinal obstruction, but in this case normal-sized lungs birth because of hypertrophy of pyloric smooth muscle.
suggest no herniated contents were present. A hiatal hernia Pyloric stenosis has features of multifactorial inheritance
from widened diaphragmatic muscular crura predisposes to with a “threshold of liability,” above which the disease is
gastroesophageal reflux, and obstruction is not a typical com- manifested when more genetic risks are present, such as
plication. Pyloric stenosis is a cause for gastric outlet obstruction family history and twin gestation. The incidence in males is
in an infant, but the onset is usually in the second or third week 1 in 200 and in females is 1 in 1000, reflecting the fact that
of life. A pharyngoesophageal (Zenker) diverticulum above the more risks must be present in females for the disease to
upper esophageal sphincter is usually a disease of adults. o ccur. Annular pancreas is a rare anomaly that can also cause
obstruction of the duodenum, and has variable age of onset,
PBD9 750 BP9 558 PBD8 765 BP8 600 but a palpable mass would not be expected. Tracheoesopha-
geal fistula, diaphragmatic hernia, and duodenal atresia are
2 F About 2% of individuals have a Meckel diverticulum, an serious conditions that are manifested at birth and are often
embryologic remnant of the omphalomesenteric duct, but only associated with multiple anomalies. Pyloric stenosis is an iso-
a small subset of these individuals have ectopic gastric mucosa lated condition that typically occurs without other anomalies.
within it, which causes intestinal ulceration. The symptoms
may mimic acute appendicitis, but appendicitis should not last PBD9 751 PBD8 766 PBD8 766 BP8 592
for 1 month or cause significant blood loss. Angiodysplasia
2 7 6 U N I T I I Diseases of Organ Systems
4 B In Hirschsprung disease, seen in 1 in 5000 live births, produce surface plaques with minimal erosion in immuno-
the aganglionic segment (either a short or long segment) of compromised persons. Diphtheria is most often a childhood
the bowel wall produces a functional obstruction with proxi- disease of upper airways, and there can be toxin-mediated sys-
mal distention. Most familial cases and some sporadic cases temic disease, including myocarditis, but there is no chronic
have RET gene mutations affecting neural crest cell migra- infection. Herpetic ulcers are sharply demarcated, and infec-
tion. Atresias are congenitally narrowed segments of bowel tion is most often found in immunocompromised persons.
(usually the small intestine) that occur with other anoma-
lies. Patients with trisomy 21 may have intestinal (usually PBD9 395, 754 BP9 558
duodenal) atresias. Complete absence of the colonic lumen
at a point of atresia is a rare congenital anomaly and is not 8 D Grand Admiral Baron Jan Gerrit van Wassenaer
a ssociated with loss of ganglion cells. Intussusception also is was attended by Dr. Herman Boerhaave in 1724, who then
a cause of bowel obstruction in infants, but it is not caused described esophageal rupture. Boerhaave syndrome may
by an aganglionic segment of bowel. Necrotizing enteroco- follow forceful vomiting, or may occur as a complication of
litis is a complication of prematurity. Volvulus is a form of instrumentation. Dissection of air from the rupture extends
mechanical obstruction that occurs from twisting of the small into soft tissue, producing the subcutaneous emphysema.
bowel on the mesentery or twisting of a segment of the colon There is no serosal barrier above the diaphragm, so esopha-
(sigmoid or cecal regions). geal contents spill into the chest cavity, producing marked
mediastinitis that is hard to treat. A stricture is likely to occur
PBD9 751–752 BP9 573–574 PBD8 766–767 BP8 600–601 with long-standing inflammation or from the fibrosis asso-
ciated with systemic sclerosis (scleroderma). Achalasia is a
5 B Caustic alkaline solutions tend to damage the esoph- functional obstruction from failure of inhibitory neurons that
agus, and may not even get as far as the stomach. If the relax the lower esophageal sphincter. Ectopia refers to tissue
esophagus is perforated, a severe mediastinitis may occur. that is out of place, most often gastric mucosa that is in the
The inflammation can resolve with scarring and stenosis, and esophagus, which can lead to esophagitis. Varices present a
that tends to affect swallowing of solids more than liquids, risk for marked bleeding.
typical for mechanical obstruction. A pharyngeal Z enker
diverticulum occurs at a point of weakness in the hypophar- PBD9 754 BP9 559 PBD8 768
ynx, most often between the inferior constrictor muscle and
cricopharyngeus muscle; it is a pulsion diverticulum from 9 E Mallory-Weiss syndrome with esophageal tears results
motility problems. Gastric lymphomas may be related to from severe vomiting. Most cases occur in the context of
Helicobacter pylori infection (MALTomas) and to immune alcohol abuse. The bleeding is usually not as life-threatening
dysregulation. Duodenal ulcerations are predominantly as varices. Absent myenteric ganglia occur with achalasia.
related to H. pylori infection. Megacolon results from marked Autoimmunity underlies scleroderma with fibrosis and
colonic inflammation or motor disturbances, and swallowed esophageal obstruction, but there is typically no bleeding.
substances are not likely to reach the colon unaltered. Herpes simplex virus infection causes ulcerations that are
usually superficial and cause pain, but do not bleed signifi-
PBD9 754 BP9 558 PBD8 767 BP8 588 cantly. Portal hypertension leads to dilation of esophageal
submucosal veins, which can bleed profusely; in this case,
6 A In achalasia, there is incomplete relaxation of the lower the patient’s age argues against the presence of cirrhosis
esophageal sphincter with lack of peristalsis. Most cases are from alcohol abuse. Widened diaphragmatic crura are pres-
“primary” or of unknown origin. They may be caused by ent with hiatal hernia that predisposes to gastroesophageal
degenerative changes in neural innervation; the myenteric reflux, and this is not associated with alcohol abuse.
ganglia are usually absent from the body of the esophagus.
There is a long-term risk of development of squamous cell PBD9 754 BP9 559 PBD8 768 BP8 586–587
carcinoma. In Barrett esophagus, there is columnar epithelial
metaplasia, but the myenteric plexuses remain intact. Reflux 10 C The “punched-out” ulcers described result from rup-
esophagitis may be associated with hiatal hernia, but myen- ture of the herpetic vesicles. Herpesvirus and Candida infec-
teric ganglia remain intact. Plummer-Vinson syndrome is a tions typically occur in immunocompromised patients, and
rare condition caused by iron deficiency anemia; it is accom- both can involve the esophagus. Aphthous ulcers (canker
panied by an upper esophageal web. Systemic sclerosis sores) also can be found in immunocompromised patients,
(scleroderma) is marked by fibrosis with stricture. but these shallow ulcers occur most frequently in the oral
cavity. Candidiasis has the gross appearance of tan-to-
PBD9 753–754 BP9 558 PBD8 768 BP8 585–586 yellow plaques. Gastroesophageal reflux disease (GERD)
can produce acute and chronic inflammation with some
7 E Chronic Chagas disease can lead to damage to not only erosion, although typically not in a sharply demarcated
myocardium but also tubular structures of the GI tract, espe- pattern; GERD has no relationship with immune status.
cially the esophagus with secondary achalasia. The organisms Mallory-Weiss syndrome results from mucosal tears of the
are hard to find microscopically, but they elicit the inflamma- esophagus, and laceration of the esophagus can occur with
tory response that damages neurons to produce the motility severe vomiting and retching.
problems. Pertussis is whooping cough, typically a childhood
disease affecting the upper airways. Candidiasis tends to PBD9 754–755 BP9 560 PBD8 768–769 BP8 580–581
C H A P T E R 1 7 Gastrointestinal Tract 2 7 7
1 1 E Esophageal dysmotility is the E in CREST, a mnemonic focal dysplasia, typical of Barrett esophagus. Patients with
that details the key findings with the limited form of systemic a focus of Barrett esophagus have a higher risk of develop-
sclerosis (scleroderma): C = calcinosis; R = Raynaud phenom- ing adenocarcinoma than the general population, particularly
enon; E = esophageal dysmotility; S = sclerodactyly; T = telan- when high-grade dysplasia is present. Achalasia refers to the
giectasias. Although scleroderma is an autoimmune disorder failure of the lower esophageal sphincter to relax, which gives
that often includes formation of anticentromere antibodies, rise to dilation of the proximal portion of the esophagus. An
little inflammation is seen by the time the patient seeks clinical epiphrenic diverticulum in the lower esophagus is not associ-
attention. There is increased collagen deposition in gastrointes- ated with Barrett mucosa, but arises from increased intralumi-
tinal submucosa and muscularis. Fibrosis may affect any part nal pressure against lower esophageal sphincter obstruction.
of the gastrointestinal tract, but the esophagus is the site most M allory-Weiss syndrome is associated with vertical lacerations
often involved. For a diagnosis of Barrett esophagus, colum- in the esophagus that may occur with severe vomiting and
nar metaplasia must be seen histologically, and there is often retching. Squamous cell carcinomas occur in the midesopha-
a history of gastroesophageal reflux disease. Hiatal hernia is gus, but they do not arise in association with Barrett esophagus.
frequently diagnosed in individuals with reflux esophagitis Instead, they are linked to smoking and alcohol consumption.
and can lead to inflammation, ulceration, and bleeding, but
formation of a stricture is uncommon. An upper esophageal PBD9 757–758 BP9 561–562 PBD8 770–771 BP8 588–589
web associated with iron deficiency anemia might produce dif-
ficulty in swallowing, but this condition is rare. Portal hyper- 15 A Adenocarcinomas of the esophagus are typically
tension gives rise to esophageal varices, not fibrosis. located in the lower esophagus, where Barrett esophagus
develops at the site of long-standing gastroesophageal reflux
PBD9 750, 753 BP9 560–561 PBD8 223–225 BP8 150 disease. Barrett esophagus is associated with an increased risk
of developing adenocarcinoma, particularly when high-grade
1 2 D Her ongoing inflammatory process results from dysplasia is present. Columnar metaplasia may progress to
reflux of acid gastric contents into the lower esophagus. Gas- dysplasia, then adenocarcinoma. Carcinoid tumors occur in
troesophageal reflux disease (GERD) is a common problem different parts of the gut, including the appendix, ileum, rec-
that stems from a variety of causes, including sliding hiatal tum, stomach, and colon. Leiomyosarcoma of the esophagus
hernia, decreased tone of the lower esophageal sphincter, is rare and is unrelated to a history of heartburn. Malignant
and delayed gastric emptying. Patients may have a history of lymphomas of the gastrointestinal tract do not commonly
heartburn after eating. Barrett esophagus is a complication occur in the esophagus and are not related to reflux esophagi-
of long-standing GERD and is characterized by columnar tis. Squamous cell carcinomas of the esophagus are most often
metaplasia of the squamous epithelium that normally lines associated with a history of chronic alcoholism and smoking.
the esophagus. There may be inflammation and mucosal
ulceration overlying varices, but this condition usually does PBD9 758–759 BP9 562 PBD8 772–773 BP8 589–591
not have heartburn as the major feature. Esophageal varices
from portal hypertension can lead to marked hematemesis. 1 6 E This large, ulcerated lesion with heaped-up margins
A rare complication of iron deficiency is the appearance of is a malignant tumor of the esophageal mucosa. There are two
an upper esophageal web (Plummer-Vinson syndrome). main histologic types of esophageal carcinomas—squamous
Progressive fibrosis with stenosis is found in scleroderma. cell carcinoma and adenocarcinoma—with distinct risk fac-
tors. Smoking and alcoholism are the primary risk factors for
PBD9 755–756 BP9 560–561 PBD8 769–770 BP8 588 esophageal squamous cell carcinoma in the Western world.
Adenocarcinoma is most likely to arise in the lower third
1 3 C Variceal bleeding is a common complication of of the esophagus and to be associated with Barrett esopha-
hepatic cirrhosis, which can be an outcome of chronic hepa- gus. Chronic inflammation may lead to stricture and not to a
titis B infection. Portal hypertension leads to dilated submu- localized mass. Dilated veins occur in esophageal varices; they
cosal esophageal veins that can erode and bleed profusely. do not produce an ulcerated mass. A dense, collagenous scar
Barrett esophagus is a columnar metaplasia that results from of the mid esophagus is uncommon, but it may occur after
gastroesophageal reflux disease (GERD). Bleeding is not a injury from ingestion of a caustic liquid. Intranuclear inclu-
key feature of this disease. Esophageal candidiasis may be sions suggest infection with herpes simplex virus or cytomeg-
seen in immunocompromised patients, but it most often pro- alovirus, both of which are more likely to produce ulceration
duces raised mucosal plaques and is rarely invasive. GERD without a mass; both occur in immunocompromised patients.
may produce acute and chronic inflammation and, rarely,
massive hemorrhage. Esophageal carcinomas may bleed, PBD9 758–759 BP9 562–563 PBD8 773–774 BP8 589–591
but not enough to cause massive hematemesis. A Zenker
diverticulum is located in the upper esophagus and results 1 7 C The Turkmen population around the Caspian Sea
from cricopharyngeal motor dysfunction; it presents a risk has the highest rate of esophageal cancer on earth, and most
for a spiration, but not for hematemesis. of these are squamous cell carcinomas arising in the mid-
esophagus. Consuming hot tea, contamination with silicates
PBD9 756–757 BP9 559 PBD8 771–772 BP8 587–588 in consumed food, micronutrient deficiencies, and family his-
tory have been implicated, as well as human papillomavirus
14 B The biopsy specimen shows residual ulcerated infection. There are no specific gene mutations known to be
squamous epithelium along with columnar metaplasia and associated with esophageal carcinoma in this population. In
2 7 8 U N I T I I Diseases of Organ Systems
contrast, tobacco use and alcohol consumption are linked to 21 A The high MCV is indicative of a megaloblastic ane-
esophageal cancers in Europe and North America. The main mia, most likely pernicious anemia, resulting from autoim-
autoimmune disease affecting the esophagus, systemic scle- mune atrophic gastritis. Delayed maturation of the myeloid
rosis (scleroderma), is not a major risk for cancer. Infectious cells leads to hypersegmentation of polymorphonuclear
agents such as Candida and herpes simplex virus do not carry leukocytes. Loss of gastric parietal cells from autoimmune
a risk for cancer; the role for human papillomavirus in this injury causes a deficiency of both intrinsic factor and acid. In
process is not well established. Reflux esophagitis is a risk for the absence of this factor, vitamin B12 cannot be absorbed in
adenocarcinomas arising in the lower third of the esophagus. the distal ileum. Among the various anti–parietal cell anti-
bodies are those directed against the acid-producing pro-
PBD9 759–760 BP9 563 PBD8 772–774 BP8 589–590 ton pump enzyme H+,K+-ATPase. Antigliadin antibodies
are found with celiac disease that does not affect the gastric
1 8 A These findings are consistent with an acute gastritis. mucosa. H. pylori causes chronic gastritis and peptic ulcer
If significant inflammation is not present, then the term disease, but does not injure parietal cells. In pernicious ane-
g astropathy is used. Heavy consumption of ethanol is probably mia, no antibodies are directed against intrinsic factor recep-
the most common cause, but aspirin and nonsteroidal anti- tor on ileal mucosal cells. Infection with Tropheryma whippelli
inflammatory drugs (NSAIDs), smoking, and chemotherapy causes Whipple disease, which may involve any organ, but
agents can produce the same findings. NSAIDs can be cofac- most often affects intestines, central nervous system, and
tors in peptic ulcer disease. Chlorpromazine (used to treat joints; malabsorption is common.
nausea) does not have the same association. Cimetidine and
omeprazole are used to treat peptic ulcer disease by reducing PBD9 764–765 BP9 567 PBD8 778–779 BP8 438–439, 592
gastric acid production, increasing the serum gastrin. Cimeti-
dine is an H2 receptor blocker, and omeprazole is a proton 22 B Helicobacter pylori organisms shown in the figure
pump inhibitor. Clindamycin is a broad-spectrum antibiotic reside in the mucus layer above the gastric mucus and are
that may alter flora in the lower gastrointestinal tract. associated with various gastric disorders, ranging from
chronic gastritis with erythema and thickened rugal folds, as
PBD9 760–762 BP9 564–565 PBD8 774–775 BP8 593 in this case, to peptic ulcers and to adenocarcinoma. H. pylori
organisms elaborate several toxic substances that injure the
19 A Prolonged use of nonsteroidal anti-inflammatory epithelium. The H. pylori gene from a pathogenicity island
drugs (NSAIDs) is an important cause of acute gastritis. encodes cytotoxin-associated antigen (CagA) and is present
NSAIDs inhibit cyclooxygenase-dependent synthesis of in many patients with chronic gastritis and peptic ulcers;
prostaglandins E2 and I2, which stimulate nearly all defense it increases the risk for gastric cancer. Cysteine proteinases
mechanisms. Excessive alcohol consumption and smoking produced by Entamoeba histolytica aid in tissue invasion.
also are possible causes. Acute gastritis tends to be diffuse Heat-stable enterotoxin is produced by strains of Escherichia
and, when severe, can lead to significant mucosal hemor- coli that cause traveler’s diarrhea. Shiga toxin is elaborated
rhage that is difficult to control. Epithelial dysplasia may by Shigella flexneri organisms, which cause a form of bacillary
occur at the site of chronic gastritis. It is a forerunner of gas- dysentery. Verocytotoxin produced by some E. coli strains
tric cancer. Infection with Helicobacter pylori is not associated is associated with hemolytic uremic syndrome mediated by
with acute gastritis. Hyperplastic polyps of the stomach do endothelial injury.
not result from acute gastritis, but may arise in association
with chronic gastritis. Acute gastritis does not increase the PBD9 763–764 BP9 566–567 PBD8 776–778 BP8 592–594
risk of gastric adenocarcinoma.
2 3 D Although they are not found in the duodenum,
PBD9 760–762 BP9 564–565 PBD8 774–775 BP8 593 Helicobacter pylori organisms alter the microenvironment of
the stomach, causing the stomach and duodenum to be sus-
20 E So-called stress ulcers, also known as Curling ulcers, ceptible to peptic ulcer disease. Virtually all duodenal pep-
can occur in patients with burn injuries. The ulcers are often tic ulcers are associated with H. pylori infection. Ulceration
small (<1 cm) and shallow, never penetrating the muscula- can extend through the muscularis and result in perforation,
ris propria, but they can bleed profusely. Similar lesions can as in this case. The other organisms listed are not related to
occur after traumatic or surgical injury to the central ner- peptic ulcer formation, but to infectious diarrheal illnesses.
vous system (Cushing ulcers). Duodenal ulcers are typically Salmonella typhi may produce typhoid fever with more sys-
peptic ulcers in individuals with Helicobacter pylori infection. temic symptoms; the marked ulceration of Peyer patches
Esophageal varices can cause massive hematemesis, but they may lead to perforation.
occur in patients with portal hypertension, caused most com-
monly by cirrhosis. Metaplastic columnar epithelium at the PBD9 763–764 BP9 566–567 PBD8 776–778 BP8 494–497
lower end of the esophagus is present in Barrett esophagus,
resulting from chronic gastroesophageal reflux disease. Ileal 2 4 C The clinical symptoms in this case suggest peptic
ulcerations and colonic ulcerations are often due to inflam- ulcer disease. In most cases, peptic ulcers are associated with
matory bowel disease that can be from infections such as Helicobacter pylori infection. These bacteria secrete urease,
shigellosis, or they may be idiopathic, as in Crohn disease. which can be detected by oral administration of urea 14C.
After drinking the labeled urea solution, the patient blows
PBD9 762 BP9 564–565 PBD8 775–776 BP8 596 into a tube. If H. pylori urease is present in the stomach, the
C H A P T E R 1 7 Gastrointestinal Tract 2 7 9
urea is hydrolyzed, and labeled carbon dioxide is detected of the gastric type of mucus cells that infiltrate the stom-
in the breath sample. In the biopsy urease test, antral biopsy ach wall diffusely. The individual tumor cells have a signet
specimens are placed in a gel containing urea and an indica- ring a ppearance because the cytoplasmic mucin pushes the
tor, and if H. pylori is present, the color changes within min- nucleus to one side. In chronic atrophic gastritis, the rugal
utes. If not properly treated, peptic ulcers can produce many folds are lost, but there is no significant scarring or shrinkage.
complications, including massive bleeding that can be fatal. Primary gastric lymphomas are less common than adenocar-
Carcinoid tumors can occur in the stomach, but they are rare cinomas; a lymphoma may be large but would not involve the
and are not related to peptic ulcer disease, which this patient stomach in a diffuse pattern. Gastrointestinal stromal tumors
has. He does not have fat malabsorption because fat absorp- tend to be bulky masses. Granulomas are rare at this site.
tion does not occur in the stomach. Peptic ulcers rarely
progress to gastric carcinoma. The stomach has numerous PBD9 771–773 BP9 570–571 PBD8 785–786 BP8 599
arterial supplies and therefore is unlikely to be affected by
focal thrombosis. Vitamin B12 deficiency can occur with auto- 2 9 F Certain gastrointestinal lymphomas that arise from
immune atrophic gastritis because intrinsic factor, which is mucosa-associated lymphoid tissue (MALT) are called MALT
required for vitamin B12 a bsorption, is produced in gastric lymphomas. Gastric lymphomas that occur in association with
parietal cells. Helicobacter pylori infection are composed of monoclonal B cells,
whose growth and proliferation depend on cytokines derived
PBD9 763–764, 766–768 BP9 568–569 PBD8 780–781 BP8 594–596 from T cells that are sensitized to H. pylori antigens. Treatment
with antibiotics eliminates H. pylori and the stimulus for B-cell
2 5 A Gastric inflammatory/hyperplastic polyps may growth. However, lesions acquiring additional mutations,
arise in the setting of Helicobacter pylori infection. They are such as p53, may become more aggressive. MALT lesions can
the most common type of gastric polyp. They may be pre- occur anywhere in the gastrointestinal tract, although they
cursors to gastric adenocarcinomas, particular lesions larger are rare in the esophagus and appendix. In H. pylori chronic
than 1.5 cm and with high-grade dysplasia. The other listed gastritis, which may precede lymphoma development, there
options are not appropriate for an infectious etiology. are lymphoplasmacytic mucosal infiltrates. Diffuse large
B-cell lymphomas and other non-Hodgkin lymphomas that
PBD9 764 BP9 569 PBD8 778 BP8 597 are not MALT lymphomas do not regress with antibiotic ther-
apy. A utoimmune gastritis is a risk for development of gastric
2 6 A There is an association of fundic gland polyps with adenocarcinoma. Crohn disease is rare in the stomach and
use of proton pump inhibitors and also with familial adeno- is not related to H. pylori infection. G astrointestinal stromal
matous polyposis (FAP); increased gastrin may drive glan- tumors are uncommon; these bulky tumors may be prolifera-
dular hyperplasia. Gastric adenomas are most common in tions of interstitial cells of Cajal, myenteric plexus cells that are
the antrum, have intestinal metaplasia with dysplasia, and thought to be the pacemaker of the gut.
are precursors to adenocarcinoma; they may occur with
FAP. Hyperplastic polyps are associated with chronic gastri- PBD9 773 BP9 567, 571 PBD8 786–787 BP8 626
tis, often from H. pylori infection. One form of hypertrophic
gastropathy is Ménétrier disease, which results from exces- 3 0 D The figure shows that the cytoplasm of the tumor
sive secretion of transforming growth factor alpha (TGF-α) cell contains small, dark, round granules with a dense core
with diffuse enlargement of gastric rugae and protein-losing (neurosecretory granules), which are characteristic of neu-
enteropathy. roendocrine cells. The gross appearance of this tumor and
its location also are characteristic of carcinoid tumors. Many
PBD9 770 BP9 569 PBD8 782–783 BP8 588–589 well-differentiated neuroendocrine tumors (carcinoids) and
other small, benign bowel tumors are discovered inciden-
27 A The most likely cause of a large mass lesion in tally; most are 2 cm or smaller. At this size they are unlikely
the stomach is a gastric carcinoma, and this lesion is an to act in a malignant fashion. The other listed cell types do
adenocarcinoma, likely the intestinal type found in the a ntral not have neurosecretory granules.
region. Adenocarcinoma is related to Helicobacter pylori
i nfection, with β-catenin mutation. The incidence of this type PBD9 773–775 BP9 571–572 PBD8 787–789 BP8 626–627
of gastric cancer has been decreasing for decades in places
where food processing methods have improved. Malignant 3 1 C Carcinoid syndrome is uncommon. It requires a
lymphomas and leiomyosarcomas are less common and tend malignant carcinoid tumor (neuroendocrine carcinoma)
to form bulky masses in the fundus. Neuroendocrine carci- that is sufficiently large, and likely metastatic, to produce
nomas are rare. Squamous cell carcinomas typically appear biogenic amines and derivatives such as 5-HIAA (a metabo-
in the esophagus. lite of serotonin). Those tumors a rising in midgut (jejunum,
ileum) are more likely to be m alignant. Neuroendocrine cells
PBD9 771–773 BP9 570–571 PBD8 784–786 BP8 598–599 are scattered throughout the gastrointestinal tract mucosa
and are neural crest derivatives. The bowel mucosa itself is
28 E The endoscopic and radiologic findings describe the an endodermal derivative, in which connective tissues are of
linitis plastica (“leather bottle”) appearance of diffuse gastric mesodermal origin.
carcinoma. Histologically, these carcinomas are composed
PBD9 774–775 BP9 571–572 PBD8 789 BP8 626
2 8 0 U N I T I I Diseases of Organ Systems
3 2 D This gastrointestinal stromal tumor (GIST) is derived vessels as well, giving rise to thrombotic occlusion of the
from the interstitial cell of Cajal, and hence of mesenchymal blood vessels that perfuse the bowel. The symptoms and
origin. Those arising in the stomach may be less aggres- signs suggest infarction of the gut. Acute appendicitis rarely
sive than those arising in the intestine, but most are KIT leads to such a catastrophic illness, unless there is perfora-
positive and amenable to tyrosine kinase inhibitor ther- tion. (The absence of free air in the radiograph argues against
apy. Some GISTs may have mutations in platelet-derived perforation of any viscus.) Acute pancreatitis can be a seri-
growth factor receptor A (PDGFRA). Antibiotic therapy to ous abdominal emergency, but the normal levels of amylase
obliterate Helicobacter pylori infection may be useful in treat- and lipase tend to exclude it. Acute cholecystitis can produce
ing MALTomas. Azathioprine and corticosteroids may be severe abdominal pain, but bloody diarrhea and absence of
employed in treating inflammatory bowel disease, but the bowel sounds (paralytic ileus) are unlikely. Pseudomembra-
greatest risk for malignancy with inflammatory bowel dis- nous colitis develops in patients receiving broad-spectrum
ease is adenocarcinoma, particularly of the colon. Cyclophos- antibiotic therapy.
phamide is a chemotherapy agent not employed in treating
GISTs. Radiotherapy is not generally effective against mes- PBD9 779–780 BP9 574–575 PBD8 791–793 BP8 601–602
enchymal malignancies.
3 6 A Hypotension with hypoperfusion from heart fail-
PBD9 775–777 BP9 572–573 PBD8 789–790 BP8 625–626 ure is a common cause of ischemic bowel in hospitalized
p atients. The ischemic changes begin in scattered areas of
33 B The patient has acute bowel obstruction, and the the mucosa and become confluent and transmural over time.
findings at surgery show bowel infarction. The most com- This can give rise to paralytic ileus and bleeding from the
mon causes in developed nations are adhesions, hernias, and a ffected regions of the bowel mucosa. A mesenteric vascu-
metastases. Adhesions are most often the result of prior sur- litis is u ncommon, but could lead to bowel infarction. Shig-
gery, as in this case, and produce “internal” hernias, where a ellosis is an infectious diarrhea that causes diffuse colonic
loop of bowel becomes trapped (incarcerated), and the blood mucosal erosion with hemorrhage. Ulcerative colitis usually
supply is compromised. Loops of bowel that b ecome trapped produces marked mucosal inflammation with necrosis, usu-
in direct or indirect inguinal hernias also can infarct. When ally in a continuous distribution from the rectum upward.
metastases are the cause, the primary site is g enerally known, Volvulus is a form of mechanical obstruction caused by
and the cancer stage is high. Primary adenocarcinomas of twisting of the small intestine on its mesentery or twisting of
the small bowel are uncommon. Crohn disease can be focal the cecum or sigmoid colon, resulting in compromised blood
and manifest with bowel obstruction, but it is uncommon supply that can lead to infarction of the twisted segment.
in p atients of this age. Intussusception can be focal, but it
is uncommon. Abdominal tuberculosis may cause circum- PBD9 779–780 BP9 574–575 PBD8 791–793 BP8 601–602
ferential stricture of the bowel, and should be considered in
regions where the prevalence of tuberculosis is high. Vol- 3 7 A Angiodysplasia refers to tortuous dilations of muco-
vulus may involve the cecal or sigmoid regions of the colon sal and submucosal vessels, seen most often in the cecum in
(because of their mobility). When volvulus involves the small patients older than 50 years. These lesions, although uncom-
intestine, torsion around the mesentery generally occurs, and mon, account for 20% of cases involving significant lower
there is extensive (not segmental) small bowel infarction. intestinal bleeding. Bleeding usually is not massive, but can
occur intermittently over months to years. This lesion is dif-
PBD9 777–778 BP9 574 PBD8 790–791 BP8 604–605 ficult to diagnose and is often found radiographically. The
focus (or foci) of abnormal vessels can be excised. Collagenous
3 4 C The infant has signs and symptoms of acute bowel colitis is a rare cause of a watery diarrhea that is typically not
obstruction. Intussusception occurs when one small segment bloody. Colonic diverticulosis can be associated with hemor-
of small bowel becomes telescoped into the immediately dis- rhage, but the outpouchings usually are seen on colonoscopy.
tal segment. This disorder can have sudden onset in infants Hemorrhoids at the anorectal junction may account for bright
and may occur in the absence of any anatomic abnormality. red rectal bleeding, but they can be seen or palpated on rectal
Duodenal atresia (which typically occurs with other anoma- examination. Mesenteric venous thrombosis is rare and may
lies, particularly trisomy 21) and Hirschsprung disease (from result in bowel infarction with severe abdominal pain.
an aganglionic colonic segment) usually manifest soon after
birth. Almost all cases of Meckel diverticulum are asymp- PBD9 780–781 BP9 576 PBD8 793 BP8 603
tomatic, although in some cases functional gastric mucosa
is present and can lead to ulceration with bleeding. Pyloric 38 C Fat malabsorption can occur from impaired intralu-
stenosis is seen much earlier in life and is characterized by minal digestion. Smelly, bulky stools containing increased
projectile vomiting. amounts of fat (steatorrhea) are characteristic. Pancreatic
or biliary tract diseases are important causes of fat malab-
PBD9 777–778 PBD8 791 sorption. Amebiasis can produce a range of findings from a
watery diarrhea to dysentery with mucus and blood in the
3 5 D The patient’s history of myocardial infarction sug- stool. Giardiasis produces mainly a watery diarrhea. Malab-
gests that he had severe coronary atherosclerosis, and the sorption with steatorrhea is unlikely to be associated with
elevated Hgb A1c suggests diabetes mellitus. Systemic bleeding. Cholera results in a massive watery diarrhea.
atheromatous disease most likely involves the mesenteric
PBD9 781 BP9 577 PBD8 794 BP8 609–610
C H A P T E R 1 7 Gastrointestinal Tract 2 8 1
39 E Characteristic serologic findings with celiac disease 4 2 E Disaccharidase (lactase) deficiency, either congenital
include positive tests for antitransglutaminase, antigliadin, or acquired, is symptomatic when the lactose in milk products
and antiendomysial antibodies. This chronic disease may is not broken down into glucose and galactose by terminal
manifest in young adulthood but may escape diagnosis. d igestion, resulting in an osmotic diarrhea and gas produc-
Women are affected more than men. Celiac disease results tion from gut flora. Affected individuals do not always make
from gluten sensitivity. Exposure to the gliadin protein in the connection between diet and symptoms, or they do not
wheat, oats, barley, and rye (but not rice) results in intestinal consume enough milk products to become symptomatic. An
inflammation. Gliadin sensitivity causes epithelial cells to autoimmune gastritis is most likely to result in vitamin B12 mal-
produce IL-15, which in turn leads to accumulation of acti- absorption. Celiac disease also is diet related and results from
vated CD8+ T cells that bear the NK cell receptor NKG2D sensitivity to gluten in some grains. Cholelithiasis can cause
and damage the enterocytes expressing MIC-A. A trial of biliary tract obstruction with malabsorption of fats and pain
a gluten-free diet is the most logical therapeutic option. in the right upper quadrant of the abdomen. Cystic fibrosis
Patients usually become symptom-free, and normal histo- affects the pancreas and mainly produces fat m alabsorption.
logic features of the mucosa are restored. Some patients
develop dermatitis herpetiformis, and a few enteropathy- PBD9 784 BP9 579–580 PBD8 797 BP8 610
associated T-cell lymphomas. Anticentromere antibody
is most specific for limited scleroderma (formerly CREST 4 3 E The clinical features suggest food poisoning caused by
syndrome) with esophageal dysmotility. The anti–DNA the ingestion of a preformed enterotoxin. Staphylococcus aureus
topoisomerase I antibody is most specific for diffuse sclero- grows in food (milk products and fatty foods are favorites)
derma, in which gastrointestinal tract involvement by sub- and elaborates an enterotoxin that, when ingested, produces
mucosal fibrosis may be more extensive, and malabsorption diarrhea within hours. Bacillus cereus is better known for grow-
may be present. Antimitochondrial antibody is more spe- ing on reheated fried rice; it produces an exotoxin that causes
cific for primary biliary cirrhosis. Antinuclear antibody is acute nausea, vomiting, and abdominal cramping. Clostridium
present in a wide variety of autoimmune diseases, but it is difficile can produce a pseudomembranous colitis in patients
not characteristic of celiac sprue. treated with broad-spectrum antibiotics. Some strains of Esch-
erichia coli can produce various diarrheal illnesses, but without
PBD9 782–783 BP9 577–579 PBD8 795–796 BP8 610–611 a preformed toxin. Salmonella enterica is most often found in
poultry products, but the diarrheal illnesses develop within 2
40 E The malabsorption responded to dietary treatment. days. Vibrio parahaemolyticus is found in shellfish.
She probably has celiac disease (gluten sensitivity) with his-
tologic features including flattening of the mucosa, diffuse PBD9 785–786 BP9 581 PBD8 357, 797 BP8 606
and severe atrophy of the villi, crypt hyperplasia, and c hronic
inflammation of the lamina propria. There is an increase in 44 D Raw or poorly cooked shellfish can be the source
intraepithelial lymphocytes, both CD4+ and CD8+. Affected of Vibrio parahaemolyticus, which tends to produce a milder
persons are HLA-DQ2 or HLA-DQ8 positive. Crypt abscesses d iarrhea than Vibrio cholerae. Vibrio organisms produce a
are nonspecific and can be seen in inflammatory bowel dis- toxin that increases adenylate cyclase, leading to chloride ion
ease. Lymphatic obstruction occurs in Whipple disease, and secretion and osmotic diarrhea. Cryptosporidium as a cause
in addition, foamy macrophages accumulate in the lamina of watery diarrhea is most often found in immunocompro-
propria. The macrophages contain PAS-positive granules mised individuals. Entamoeba histolytica produces colonic
that under electron microscopy show an actinomycete called mucosal invasion along with exudation and ulceration;
Tropheryma whippelli. Noncaseating granulomas are found in stools contain blood and mucus. Staphylococcus aureus can
the intestinal wall in Crohn disease. produce food poisoning through elaboration of an entero-
toxin that causes an explosive vomiting and diarrhea within
PBD9 782–783 BP9 577–579 PBD8 795–796 BP8 610–611 2 hours after ingestion. Yersinia enterocolitica is invasive and
can produce extraintestinal infection.
4 1 B Environmental enteropathy affects millions of
children worldwide. Recurrent infection sets up a cycle of PBD9 785–786 BP9 582 PBD8 797 BP8 606–607
m ucosal injury and inflammatory response that produces
an appearance similar to celiac disease. There is no single 4 5 B The source of Campylobacter jejuni can include con-
infectious agent implicated, but likely there are many patho- taminated water, unpasteurized milk, and poorly cooked
gens that cumulatively contribute to mucosal damage. poultry. The bloody diarrhea (dysentery) and leukocytes
Abetalipoproteinemia is a rare condition from mutations in suggest intestinal mucosal invasion by a bacterial organ-
microsomal triglyceride transfer protein that impairs entero- ism. An ascending paralysis (Guillain-Barré syndrome) may
cyte transport of lipoproteins. Cystic fibrosis results from complicate some Campylobacter infections because of cross-
CFTR gene mutations affecting chloride ion channels, but reactivity between human ganglioside GM1 and bacterial
the resultant diarrhea is primarily from loss of pancreatic lipopolysaccharide. Bacillus cereus food poisoning tends to
function. The most common disaccharidase deficiency is lac- produce abrupt onset of vomiting. Clostridium perfringens
tase deficiency, with milk intolerance. NOD2 gene mutations tends to produce gas gangrene. Giardiasis produces a watery
may contribute to Crohn disease. diarrhea without dysentery or extraintestinal complications.
Rotavirus infections are most common in children.
PBD9 783–784 BP9 579 PBD8 796 BP8 611
PBD9 786–787 BP9 582–583 PBD8 799–800 BP8 606–608
2 8 2 U N I T I I Diseases of Organ Systems
46 E Infection by one of several Salmonella enterica (not voluminous d iarrhea suggests small intestinal involvement.
Typhi) causes a self-limited diarrhea. This is a form of food The lack of leukocytes makes bacterial infection less likely.
poisoning, typically from contaminated poultry products. Cytomegalovirus infections are more likely in immunocompro-
Bacillus cereus growing in foods such as reheated fried rice mised persons. Botulism leads to paralysis from a n eurotoxin.
produces an exotoxin, which, on ingestion, can produce acute Staphylococcal food poisoning tends to be abrupt in onset and
onset of nausea, vomiting, and abdominal pain. Amebiasis of short duration. Strongyloidiasis tends to persist for months
from Entamoeba histolytica can be an invasive, exudative to years. Cholera produces life-threatening fluid loss.
infection. The stools contain blood and mucus. Various dis-
eases result from contamination with different strains of PBD9 792–793 BP9 585 PBD8 804 BP8 606
Escherichia coli, based on the characteristics of the organisms,
and whether they invade or produce an enterotoxin. Poultry 50 F Rotavirus is the most common cause of viral gastro-
products are usually not contaminated with E. coli. Rotavi- enteritis in children. It is a self-limited disease that affects
rus is most likely to produce symptomatic watery diarrhea mostly infants and young children, who can lose a significant
in children, unrelated to diet. Staphylococcus aureus causes an amount of fluid relative to their size and can quickly become
acute onset of abdominal pain, bloating, and diarrhea, not by dehydrated. The death rate is less than 1%. Campylobacter
directly infecting the gastrointestinal tract, but by producing jejuni is more often seen in children and adults as a food-borne
an exotoxin while growing on food that is subsequently cause of fever, abdominal pain, and diarrhea. Cryptosporidi-
ingested. Yersinia enterocolitica is most often found in con- osis most often causes a watery diarrhea in immunocompro-
taminated milk or pork products and may disseminate to mised adults. Enterohemorrhagic strains of Escherichia coli
produce lymphadenitis and further extraintestinal infection. can produce hemolytic uremic syndrome in young children.
Listeriosis can be a congenital infection that is present along
PBD9 788–789 BP9 583–584 PBD8 801 BP8 606–608 with meningitis and sepsis at birth; in infants, children, and
adults, it is a food-borne or water-borne infection that tends
4 7 D Typhoid fever begins as an intestinal infection, but it to occur in epidemics. Norwalk virus is a common cause of
becomes a systemic illness. A chronic carrier state can occur in diarrheal illness in adults. Shigellosis produces dysentery
some infected individuals, with colonization of the gallblad- with bloody diarrhea.
der. Campylobacter jejuni may produce dysentery, but gener-
ally not systemic disease. Clostridium perfringens can cause PBD9 793 BP9 585 PBD8 804 BP8 605–606
gas gangrene. Mycobacterium bovis is now rare because of pas-
teurization of milk products; it was best known as a cause of 5 1 A Hookworm infections may be caused by Ancylos-
bowel obstruction from circumferential ulceration and scar- toma duodenale (Old World) or Necator americanus (New
ring of the small bowel. Shigellosis can produce dysentery, World) or both, b ecause the geographic distributions may
but the infection is generally limited to the colon. Infection overlap, particularly in Africa and Asia. The sharp hooks of
with Yersinia enterocolitica can produce extraintestinal infec- the worms penetrate the small intestinal mucosa and pro-
tion with lymphadenitis, but generally not d ysentery. duce bleeding. The worms live for months to years. Infection
occurs through the skin, and larval development occurs in
PBD9 789 BP9 584 PBD8 801–802 BP8 608 the lungs until migration to the trachea and swallowing con-
ducts the worms to the duodenum. Organisms listed in the
4 8 D The opened colon shows pseudomembranes that are remaining choices are unlikely to produce significant gastro-
patches of fibrinopurulent debris attached to the mucosa. intestinal hemorrhage.
Pseudomembranous enterocolitis is a complication of broad-
spectrum antibiotic therapy, which alters gut flora to allow PBD9 794 BP9 585 PBD8 805–806
overgrowth of Clostridium difficile or other organisms that
are capable of inflicting mucosal injury. Clostridium septicum 5 2 D Diarrhea with mucus and blood in the stools may be
infection can lead to myonecrosis that is most often associ- caused by several enteroinvasive microorganisms, including
ated with malignancy or immunosuppression. An inflamma- Shigella dysenteriae and Entamoeba histolytica. In most cases,
tory bowel disease does not typically produce a pronounced the diarrhea is self-limited. The initial episode of diarrhea
exudate and is not associated with C. difficile. This gross pat- could have been caused by one of several organisms; how-
tern also can appear from ischemic injury that is vascular or ever, the occurrence of a liver abscess after an episode of
mechanical, but this patient’s history and the time course diarrhea most likely results from infection with E. histolytica.
support an iatrogenic cause. An ischemic colitis resulting Colonic mucosal and submucosal invasion by E. histolytica
from mesenteric artery thrombosis could appear similar, but allows the organisms to access the submucosal veins drain-
it is not associated with C. difficile. A dilated, thinned, toxic ing to the portal system and the liver. Clostridium difficile
megacolon is an uncommon complication of ulcerative colitis. causes pseudomembranous colitis after antibiotic therapy.
Dissemination of Cryptosporidium and Strongyloides organ-
PBD9 791 BP9 584–585 PBD8 803 BP8 608 isms may occur in immunocompromised patients. Giardia
produces a self-limited, watery diarrhea.
4 9 C Norovirus outbreaks result from contamination of
food or water, most often in venues where multiple persons PBD9 787–788, 794–795 BP9 583 PBD8 800–801 BP8 606–607
congregate. Was it the resort pool? Noroviruses, as well as
the Giardia parasite, are resistant to chlorination. Was it the 53 B The ileum shows chronic inflammation with lym-
buffet? Salads, shellfish, and meats are often implicated. The phoid aggregates. The inflammation is transmural, affecting
C H A P T E R 1 7 Gastrointestinal Tract 2 8 3
the mucosa, submucosa, and muscularis as shown in the pathogenesis of ulcerative colitis is unclear, but is most likely
figure. During surgery, inflammation is also observed in the mediated by a T-cell response to an unknown antigen (but
serosa. A deep fissure extending into the muscularis is pres- not a gut infection), leading to an imbalance between T-cell
ent. These histologic features are highly suggestive of Crohn activation and regulation. The TH17 immune response has
disease. Extension of fissures into the overlying skin can pro- CD4+ T cells present in the lesions that secrete damaging
duce enterocutaneous fistulas, although enteroenteric fistu- substances. Autoantibodies against tropomyosin are pres-
las between loops of bowel are more common. Although the ent, but do not play a pathogenic role in ulcerative colitis.
risk of adenocarcinoma is increased in Crohn disease, this Mutations in the NOD2 gene are linked to Crohn disease,
complication is less common than sequelae of inflamma- not ulcerative colitis. Inheritance of a germline APC muta-
tion. Intussusception may occur when there is a congenital tion causes familial adenomatous polyposis with a very high
or acquired obstruction in the bowel. Hepatic abscess can risk for colon cancer. Ulcerative colitis also increases the risk
follow amebic colitis, or other infections. Mesenteric artery for colon cancer, but not secondary to APC gene mutation.
thrombosis, typically a complication of atherosclerosis, is
unlikely in a 27-year-old man. PBD9 796–798, 800 BP9 588–591 PBD8 811–812 BP8 614–616
PBD9 796–800 BP9 587–590 PBD8 808–811 BP8 611–614 57 B The findings in Crohn disease and ulcerative colitis
overlap, and in at least 10% of cases it may be impossible to
5 4 D Irritable bowel syndrome (IBS) can be difficult to differentiate between them—a so-called indeterminate coli-
diagnose because of protean manifestations found in many tis. Regardless of the exact diagnosis, there is a considerable
other conditions. No pathologic or physiologic abnormali- increase in risk for development of carcinoma 8 to 10 years
ties can be identified reliably with IBS. Patients may benefit after disease onset. Surveillance screening can detect dyspla-
from behavioral therapies. Placebos may work as well as sia as a precursor to carcinoma, but would you just remove
pharmacotherapies. The lack of an increased stool fat in this the colon with the ongoing problem and avoid missing the
case indicates that chronic pancreatitis and cystic fibrosis are possible cancer? If you remove the colon, but it turns out to
unlikely. Diverticular disease is more likely to occur in older be Crohn disease, it may recur. Extraintestinal manifestations
adults. Inflammatory bowel disease has both pathologic and may occur regardless. Doctors like to go for the win with a
radiographic findings. Viral gastroenteritis is unlikely to per- “cure,” but patients want to avoid potential loss of life or func-
sist for 5 years. tion. The doctor gets to walk away from any outcome, but the
patient does not. There are often no easy answers in medicine.
PBD9 796 BP9 580 PBD8 807 BP8 606
PBD9 800–802 BP9 589–591 PBD8 812–813 BP8 612–616
5 5 A The figure shows a diffuse, predominantly mono-
nuclear infiltrate in the lamina propria along with a crypt 58 B The clinical and histologic features are consistent
abscess. Ulcerative colitis can lead to relapsing and remit- with Crohn disease, one of the idiopathic inflammatory
ting episodes of low volume diarrhea containing blood and bowel diseases. Crohn disease is marked by segmental bowel
mucus and diffuse inflammation and ulceration of the rectal involvement and transmural inflammation that leads to stric-
and colonic mucosa. One of the most dreaded complications tures, adhesions, and fistula. Ulcerative colitis has mucosal
of ulcerative colitis is the development of colonic adenocar- involvement extending variable distances from the rectum.
cinoma. There is a twentyfold to thirtyfold higher risk in In contrast to Crohn disease, the mucosal involvement is dif-
patients who have had ulcerative colitis for 10 or more years fuse and does not show “skip areas.” Fissures and fistulas
compared with control populations. Diverticulitis can pro- are not frequently seen in ulcerative colitis. The findings in
duce abdominal pain and blood in the stool, but there is no Crohn disease and ulcerative colitis overlap, and in at least
association with ulcerative colitis. Fat malabsorption usually 10% of cases it may be impossible to differentiate between
does not occur in ulcerative colitis because the ileum often is them—a so-called indeterminate colitis. Generally, crypt
not involved. Perirectal fistula formation is more typical of abscesses are more typical of ulcerative colitis, and granu-
Crohn disease, in which there is transmural inflammation. lomas are more typical of Crohn disease, but these features
Ulcerative colitis is associated with several extraintestinal are not present in most biopsy specimens from patients with
manifestations, including sclerosing cholangitis, but it has either condition. A story is told of an attending physician at
no relationship to primary biliary cirrhosis. Pseudomembra- an academic m edical center who was known to berate stu-
nous colitis is caused by Clostridium difficile infections associ- dents and residents on rounds for not definitively diagnos-
ated with broad-spectrum antibiotic treatment. ing ulcerative colitis and Crohn disease. When he retired,
incomplete records for patients with idiopathic inflamma-
PBD9 796–798, 800 BP9 587–591 PBD8 811–812 BP8 614–616 tory bowel disease were found in his office; the records rep-
resented about one sixth of the total cases of inflammatory
56 C The segment of the colon shows the diffuse and bowel disease that he had seen. Amebiasis and shigellosis are
severe ulceration characteristic of ulcerative colitis. The infectious processes that can cause mucosal ulceration, but
inflammation shown is so severe that areas of mucosal they do not produce granulomas or fissures. Sarcoidosis can
ulceration have produced pseudopolyps or islands of residual involve many organs and give rise to noncaseating granulo-
mucosa. Ulcerative colitis is a systemic disease; in some mas; however, involvement of the intestines is uncommon,
patients, it is associated with migratory polyarthritis, anky- and sarcoidosis does not give rise to ulcerative disease.
losing spondylitis, and primary sclerosing cholangitis. The
PBD9 796–800 BP9 589–591 PBD8 808–811 BP8 612–614
2 8 4 U N I T I I Diseases of Organ Systems
59 B These are findings of idiopathic inflammatory bowel 6 3 A The figure shows a large villous adenoma. There is a
disease most likely to be Crohn disease. The ileal involvement high probability that large villous adenomas will progress to
accounts for the vitamin K and vitamin B12 deficiencies as well invasive adenocarcinoma. When they occur in the descend-
as disrupted enterohepatic circulation of bile salts predispos- ing colon, these lesions are annular and cause obstruction.
ing to gallstone formation. The inflammatory response in In the colon, non-Hodgkin lymphomas are far less common
Crohn disease may result from inappropriate innate immune than adenocarcinomas, and they do not manifest as mucosal
responses to gut flora, as discussed in the text. Angiodyspla- sessile masses. Carcinoid tumors are typically small and yel-
sia leads to bleeding from abnormal submucosal vessels, most lowish, and most grow slowly. Leiomyosarcomas are rare;
often in the cecum of older adults. Diverticular disease is com- they produce large bulky masses, but they do not arise on
mon in older persons but results from mechanical, not immune, the mucosa. Mucinous cystadenomas are cystic and are more
mechanisms. Severe peripheral atherosclerosis may cause isch- likely to arise in an ovary or in the pancreas. The original
emic bowel disease, but this is usually an acute process. lesion in this patient was a villous adenoma.
PBD9 796–800 BP9 589–590 PBD8 808–811 BP8 611–612 PBD9 808–809 BP9 594–595 PBD8 819–820 BP8 617–618
6 0 C Colonic diverticulosis may be accompanied by 64 A This young patient’s colon shows hundreds of pol-
intermittent minimal bleeding and, rarely, by severe bleeding. yps. This is most likely a case of familial adenomatous pol-
One or more diverticula may become inflamed (diverticuli- yposis (FAP) syndrome, which results from inheritance of
tis) or, less commonly, may perforate to produce an abscess, one mutant copy of the APC tumor-suppressor gene (a few
peritonitis, or both. Diverticular disease is not a premalignant FAP cases are associated with DNA mismatch repair genes).
condition. The diverticula project outward, and even with Every somatic cell of this patient most likely has one defec-
inflammation, luminal obstruction is unlikely. Malabsorption tive copy of the APC gene. Polyps are formed when the sec-
is not a feature of diverticular disease. Toxic megacolon is an ond copy of the APC gene is lost in many colon epithelial
uncommon complication of inflammatory bowel disease. cells. Without treatment, colon cancers arise in 100% of these
patients because of accumulation of additional mutations in
PBD9 803–804 BP9 586–587 PBD8 814–815 BP8 603–604 one or more polyps, typically before 30 years of age. Patients
with a gene for hereditary nonpolyposis colorectal carci-
61 C Juvenile polyps are the most common form of ham- noma, such as MLH1 and MSH2, also have an inherited sus-
artomatous polyp. Singly they are likely to be sporadic, and ceptibility to develop colon cancer, but in contrast to patients
the only complication is rectal prolapse; but when multiple with FAP, they do not develop numerous polyps. Sporadic
polyps are present, they may be the result of an autosomal colon cancers may have CpG island hypermethylation along
dominant syndrome with risk for development of adenocar- with KRAS mutations, whereas others have p53 mutations,
cinoma. The remaining choices include polyposis syndromes but the somatic cells of patients with these cancers do not
unlikely to appear at this age. show abnormalities of these genes. NOD2 mutations are
linked with Crohn disease.
PBD9 805–806 BP9 592 PBD8 816–817 BP8 617–618
PBD9 809–810 BP9 595–596 PBD8 820–822 BP8 619
6 2 A The figure shows a solitary pedunculated adenoma
of the colon with no evidence of malignancy. High mag- 65 D Of the conditions listed, the one most likely to lead
nification shows a small focus of dysplastic, non–mucin- to adenocarcinoma in a patient of this age is hereditary
secreting epithelial cells lining a colonic crypt, giving rise nonpolyposis colorectal cancer, or Lynch syndrome. Crohn
to “tubular” architecture. Such a small (<2 cm), solitary, disease is unlikely because the patient has not had prior seri-
tubular adenoma is unlikely to harbor a focus of malig- ous illness, and Crohn disease of long duration is unlikely
nancy; a search for metastases is unwarranted. Such colonic to remain asymptomatic. Although adenocarcinoma may
adenomas are more likely to occur in older persons; hence complicate Crohn disease, it does not occur as frequently
the recommendation for colonoscopy screening after age as in ulcerative colitis. This explains why colectomy is o ften
50. Removing such an adenoma does not leave the chance p erformed for ulcerative colitis, but bowel resections are
for further growth of the lesion with possible develop- avoided, if possible, in Crohn disease. The other conditions
ment of adenocarcinoma. Individuals who inherit a mutant listed are not premalignant.
APC gene usually develop hundreds of polyps at a young
age; this patient does not need genetic testing for a somatic PBD9 810 BP9 596 PBD8 821–822 BP8 621–622
mutation in the APC gene. Patients with hereditary nonpol-
yposis colorectal cancer, with multiple polyps present, have 66 B The lesion is an adenocarcinoma, showing irregular
an increased risk of endometrial cancer and develop colon glands infiltrating the muscle layer. Such a lesion in a 30-year-
cancer at a young age. It is unlikely that the blood loss from old man strongly indicates a hereditary predisposition. One
a small polyp would be sufficient to cause iron deficiency, hereditary form of cancer is called hereditary nonpolyposis
although the small amount of blood emanating from colonic colorectal cancer (HNPCC) and results from defective DNA
polyps and cancers is the rationale to test for fecal occult mismatch repair genes. As a result, mutations accumulate
blood. Peutz-Jehgers syndrome is associated with develop- in microsatellite repeats (microsatellite instability) that lead
ment of hamartomatous polyps in the small intestine. to loss of transforming growth factor beta (TGF-β) receptor-
mediated control of colonic epithelial cell proliferation and
PBD9 807–809 BP9 593–595 PBD8 819–820 BP8 618–619
C H A P T E R 1 7 Gastrointestinal Tract 2 8 5
loss of proapoptotic BAX protein enhancing survival of these of mechanical bowel obstruction; they occur suddenly in
transformed cells. He could have taken NSAIDs that inhibit adults and are surgical emergencies.
COX-2 expressed in most colonic adenomas and carcinomas.
In contrast to familial adenomatous polyposis syndrome, PBD9 815 BP9 576 PBD8 826 BP8 603
HNPCC does not lead to the development of hundreds of pol-
yps in the colon. Detection of ERBB2 (HER2/NEU) expression 6 9 F Acute appendicitis can be accompanied by an
is important in breast cancers. Germline inheritance of the e levated WBC count with neutrophilia and left shift. This is
tumor suppressor gene RB1 predisposes to retinoblastoma helpful but not decisive, and the decision to operate must be
and osteosarcoma, not colon carcinoma. E-cadherin is based on clinical judgment. Amebiasis is most likely associ-
required for intercellular adhesion; its levels are reduced, not ated with a history of diarrhea, often with blood in the stool.
increased, in carcinoma cells. Translocation of the retinoic Hyperamylasemia occurs in acute pancreatitis. Diarrhea
acid receptor alpha gene is characteristic of acute promyelo- with fluid loss and dehydration can lead to hypernatremia.
cytic leukemia. The serum carcinoembryonic antigen level may be increased
in patients with colonic cancers; however, this test is not spe-
PBD9 810 BP9 596 PBD8 821–822 BP8 622–623 cific for colon cancer. The alkaline phosphatase level may be
increased in biliary tract obstruction.
67 D The figure shows an encircling mass that is typical
of adenocarcinoma of the descending colon. Such cancers PBD9 816 BP9 600–601 PBD8 826–827 BP8 628
likely to obstruct, but they can also bleed a small amount over
months to years, causing iron deficiency anemia. The APC 70 A Pseudomyxoma peritonei (PP) is described here. It
gene, a negative regulator of β-catenin in the WNT signaling may arise from low-grade mucinous adenocarcinoma of the
pathway, is associated with familial adenomatous polyposis appendix, which may be so differentiated that it resembles an
syndrome and most sporadic colon cancers, as in this case. appendiceal mucocele. However, PP tends to recur. In women,
This pathway also is known as the adenoma-carcinoma sequence PP needs to be distinguished from mucinous tumors of the
because the carcinomas develop through an identifiable ovary. Mucinous tumors may also arise in the pancreas, but
series of molecular and morphologic steps. Loss of the PTEN are less likely to disseminate through the peritoneal cavity.
tumor suppressor gene is seen in endometrial carcinomas not Malignancies arising in the small intestine are rare. Mucin-
associated with colon carcinoma and with some hamartoma- producing malignancies of the stomach are most likely to have
tous polyps of the colon. Evidence for an additional cancer, a signet ring cell pattern and diffusely infiltrate the gastric wall.
such as an endometrial cancer, would suggest an inherited
mutation in one of the DNA mismatch repair genes, such PBD9 816, 1027 BP9 601 PBD8 828 BP8 629
as MSH2 and MLH1. Homozygous loss of these genes can
give rise to right-sided colon cancer and endometrial cancer. 71 F Spontaneous bacterial peritonitis is an uncommon
Such a mutation is typically associated with microsatellite complication found in about 10% of adult patients with cir-
instability. Infection with some strains of human papilloma- rhosis of the liver and ascites. The ascitic fluid provides an
virus leads to RB1 protein inactivation and development of excellent culture medium for bacteria, which can invade the
cervical carcinoma. Mutation with activation of KIT tyrosine bowel wall or spread hematogenously to the serosa. Spon-
kinase activity occurs in gastrointestinal stromal tumors, taneous bacterial peritonitis also can occur in children, par-
which respond well to treatment with imatinib mesylate, a ticularly children with nephrotic syndrome and ascites. The
tyrosine kinase inhibitor also used to treat chronic myelog- most common organism cultured is Escherichia coli. Appen-
enous leukemia. dicitis has a peak incidence in younger patients; the pain
is often (but not always) more localized in the right lower
PBD9 810–814 BP9 597–600 PBD8 822–825 BP8 622–624 quadrant, and ascites is usually absent. Appendicitis is not
related to alcoholism. Collagenous colitis is uncommon; it
68 B Hemorrhoids are a common problem that can stem most often leads to watery diarrhea in middle-aged women.
from any condition that increases venous pressure and Diverticulitis with rupture could produce peritonitis, but
causes dilation of internal or external hemorrhoidal veins there is typically no ascites, and diverticulitis is not related
above and below the anorectal junction. Angiodysplasia to alcoholism. Ischemic colitis may produce infarction with
of the colon leads to intermittent hemorrhage, typically in rupture and peritonitis, but ascites is usually lacking, and
older individuals. Ischemic colitis is rare in young individu- individuals with chronic alcoholism are unlikely to have
als because the most common underlying cause (severe ath- marked atherosclerosis. Pseudomembranous colitis is a com-
erosclerotic disease involving mesenteric vessels) occurs in plication of antibiotic therapy.
older patients. Intussusception and volvulus are rare causes
PBD9 817 PBD8 828
18C H A P T E R
Liver and Biliary Tract
PBD9 Chapter 18 and PBD8 Chapter 18: Liver and Biliary Tract
BP9 Chapter 15 and BP8 Chapter 16: Liver, Gallbladder, and Biliary Tract
1 A previously healthy, 38-year-old woman has become 4 A 57-year-old woman has had increasing abdominal
increasingly obtunded in the past 4 days. On physical exami- enlargement for 6 months. During the past 2 days, she devel-
nation, she has scleral icterus, abdominal fluid wave, and oped a high fever. On physical examination, her temperature is
asterixis. She is afebrile, and her blood pressure is 110/55 mm 38.5° C. The abdomen is enlarged and diffusely tender, and
Hg. Laboratory findings show a prothrombin time of 38 sec- there is a fluid wave. Paracentesis yields 500 mL of cloudy
onds (INR 3.1), serum ALT of 1854 U/L, AST of 1621 U/L, yellowish fluid. The cell count is 532/μL with 98% neutrophils
albumin of 1.8 g/dL, and total protein of 4.8 g/dL. Serum or and 2% mononuclear cells. A blood culture is positive for
blood levels of which of the following will most likely be Escherichia coli. The representative gross appearance of her
abnormal in this patient? liver is shown in the figure. Which of the following underlying
A Alkaline phosphatase diseases most commonly accounts for these findings?
B Ammonia A α1-Antitrypsin deficiency
C Amylase B Chronic alcohol abuse
D Anti-HCV C Hepatitis E viral infection
E Antinuclear antibody (ANA) D Hereditary hemochromatosis
E Primary sclerosing cholangitis
2 A pathologic study of hepatic cirrhosis is performed.
There is collapse of reticulin with bridging fibrosis from depo-
sition of collagen in the space of Disse to form fibrous septae.
Which of the following cell types is activated under the influ-
ence of cytokines to give rise to collagen-producing cells?
A Bile duct cell
B Endothelial cell
C Hepatocyte
D Macrophage
E Stellate cell
3 A 54-year-old woman has a long history of chronic hep-
atitis B infection and has had increasing malaise for the past
year. She was hospitalized 1 year ago because of upper gas-
trointestinal hemorrhage. Physical examination now shows a
firm nodular liver. Laboratory findings show a serum albumin
level of 2.5 g/dL and prothrombin time of 28 seconds. Which
of the following additional physical examination findings is
most likely to be present in this woman?
A Caput medusae
B Diminished deep tendon reflexes
C Distended jugular veins
D Papilledema
E Splinter hemorrhage
286
C H A P T E R 1 8 Liver and Biliary Tract 287
5 A study of patients with ascites includes measurements 9 A 58-year-old woman has experienced gradually
of serum and ascitic fluid protein levels. The serum-ascites increasing malaise, icterus, and loss of appetite for the
albumin gradient (SAAG) is calculated. Some patients are past 6 months. On physical examination, she has general-
found to have a high gradient, along with splenomegaly. They ized jaundice and scleral icterus. She has mild right upper
are found to have serum albumin less than 2.5 g/dL Which quadrant tenderness; the liver span is normal. Laboratory
of the following conditions is most likely to produce a SAAG studies show total serum bilirubin of 7.8 mg/dL, AST of 190
greater than 1.1? U/L, ALT of 220 U/L, and alkaline phosphatase of 26 U/L.
A Budd-Chiari syndrome A liver biopsy is done, and microscopic examination shows
B Cirrhosis the findings in the figure, along with portal bridging fibro-
C Nephrotic syndrome sis. These findings are most typical of which of the following
D Pancreatitis conditions?
E Peritonitis A Choledocholithiasis
B Congestive heart failure
6 A 65-year-old man with a history of alcohol abuse has C HAV infection
had hematemesis for the past day. Physical examination D HCV infection
reveals mild jaundice, spider angiomas, and gynecomastia. E Hemochromatosis
He has mild pedal edema, normal jugular venous pulsation F Sclerosing cholangitis
(JVP), and a massively distended abdomen. Paracentesis
is performed and the fluid obtained shows accumulation of 10 A 27-year-old man develops malaise, fatigue, and loss
protein-poor fluid that is free of inflammatory cells. Which of of appetite three weeks after a meal at the Trucker’s Cafe. He
the following factors is most likely to be responsible for the notes passing dark urine. On physical examination, he has
collection of abdominal fluid in this man? mild scleral icterus and right upper quadrant tenderness.
A Congestive heart failure Laboratory studies show serum AST of 62 U/L and ALT of
B Hepatopulmonary syndrome 58 U/L. The total bilirubin concentration is 3.9 mg/dL, and
C Hyperbilirubinemia the direct bilirubin concentration is 2.8 mg/dL. His symptoms
D Portosystemic shunts abate over the next 3 weeks. On returning to the cafe, he finds
E Splanchnic arterial vasodilation that the city’s health department has closed it. Which of the
following serologic test results is most likely to be positive in
7 A 59-year-old man has had increasing dyspnea on exer- this patient?
tion for the past year. His dyspnea is worse in the upright A Anti-HAV
position and diminishes when he is recumbent. On physical B Anti-HBc
examination he has clubbing of the fingers. Exercise induces C Anti-HBs
a decrease in his Po2 that improves when he stops and lies D Anti-HCV
down. Which of the following liver abnormalities is he most E Anti-HDV
likely to have?
A Biliary obstruction
B Chronic inflammation
C Cirrhosis
D Metastases
E Steatosis
8 A 50-year-old man has a history of chronic alcoholism,
but he stopped drinking alcohol 10 years ago. He has been tak-
ing no medications. On physical examination, he is afebrile.
The abdomen is not enlarged, and there is no tenderness. The
liver span is normal. Serologic test results for hepatitis A, B,
and C are negative. The hematocrit is 35%. Which of the fol-
lowing morphologic features is most likely to be present in his
liver?
A Concentric “onion-skin” bile duct fibrosis
B Hepatic venous thrombosis
C Interface hepatitis
D Massive hepatocellular necrosis
E Periportal PAS-positive globule deposition
F Portal fibrosis with regenerative nodules
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